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Most of us have woken up with a headache, achy back, or a low-grade fever and rummaged through the medicine cabinet looking for an over-the-counter solution. And you’ve probably had more than one to choose from, including acetaminophen (the active ingredient in Tylenol) and ibuprofen (the active ingredient in Advil and Motrin). But which one is the right choice for your health issue?

While both medications can relieve pain and reduce fevers, the science suggests there are times when one may have an advantage over the other. We spoke to health experts and looked at current research to help you decide.

If you have a headache

Both acetaminophen and ibuprofen can be used to treat headaches.

But the two medications have different mechanisms of action. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a class that includes naproxen (Aleve) and aspirin. These medications block enzymes that produce prostaglandins, which are pain- and inflammation-causing compounds released by the body in response to injury.

So in addition to treating pain and fever, ibuprofen is a better choice for pain accompanied by inflammation and swelling.

Acetaminophen works better for pain that is not primarily caused by inflammation, such as headaches.

And because it generally has fewer cardiovascular, gastrointestinal, and kidney-related side effects and fewer drug interactions than ibuprofen, it may be a better option for some older people, those with certain cardiovascular or gastrointestinal conditions or those taking certain medications, said Gabriel Gavrilescu, chair of internal medicine and geriatrics at Cleveland Clinic in Florida.

Adults can take 650 mg of regular-strength acetaminophen every four to six hours as needed or 1,000 mg of extra-strength acetaminophen every six hours, not to exceed 4,000 mg per day. However, some experts recommend a maximum limit that’s lower. “For the elderly or people of lower weight, probably 2,000 to 3,000 milligrams would be a safer limit,” Gavrilescu said.

Acetaminophen is generally safe for most people if you stick with the recommended amounts. However, taking too much — more than 4,000 mg per day — can cause severe liver damage, even liver failure. It should not be combined with heavy alcohol use, and people taking medications that affect liver function should check with their doctor before using it.

If you have muscle aches

Because it helps reduce inflammation, ibuprofen may be more effective for muscle aches, toothaches, joint pain or acute injuries such as sprains and strains, said Amber Borucki, an anesthesiologist and pediatric pain medicine specialist at Stanford Medicine Children’s Health.

Adults can take 200 to 400 mg of ibuprofen — preferably with food — every four to six hours, not to exceed up to 1,200 mg per day.

To manage more severe or persistent pain, it can also be combined with acetaminophen for short-term use (typically less than a week), with each medication taken every 6 hours and staggering so that a dose of one or the other is taken every three hours, Borucki said.

And for acute pain — such as pain after surgery — the combination of acetaminophen and ibuprofen can provide more effective pain control than taking either one alone, research shows.

In some cases, healthcare providers may prescribe higher doses of ibuprofen. Both ibuprofen and acetaminophen can be used longer-term to manage chronic pain, with close monitoring by a provider. But in general, experts recommend using the lowest effective dose for the shortest duration possible.

If you have joint pain

Some studies have found that NSAIDs, including ibuprofen, may provide greater pain relief than acetaminophen for some people with osteoarthritis, the most common type of arthritis, which often occurs with aging and causes joint pain.

In cases of chronic inflammatory pain that requires ongoing treatment — such as osteoarthritis or rheumatoid arthritis, an autoimmune condition — a doctor may recommend a selective NSAID, which is a prescription medication such as celecoxib that selectively blocks the COX-2 enzyme involved in inflammation. This may reduce pain and inflammation while also potentially lowering the risk of gastrointestinal side effects, such as ulcers, compared with traditional NSAIDs, Borucki said. Selective NSAIDs carry other risks, however, including cardiovascular events and other potential complications for some people with certain medical conditions.

Gavrilescu said he also recommends topical NSAIDs such as diclofenac (which can be applied to the skin in a patch, gel, spray, or cream) for chronic joint pain because they may reduce the risk of systemic side effects compared with oral NSAIDs, and he often encourages people to address the underlying cause of persistent pain and discomfort with physical therapy or other nonmedicinal treatments.

If you have a cold or flu

Both acetaminophen and ibuprofen can help relieve symptoms related to a cold, COVID, flu, or any other respiratory infection. However, one medication may work better than the other, depending on your symptoms.

Ibuprofen is often preferred for sore throats to help reduce pain associated with throat swelling. For fevers and related body aches, on the other hand, either acetaminophen or ibuprofen can be taken alone or together, alternating them to help control fever and pain while reducing the need for high doses of either medication, Gavrilescu said.

Keep in mind that many other over-the-counter pain relievers, cold and flu medications, and even opioids also contain acetaminophen. When taking acetaminophen along with combination drugs intended to treat nasal congestion, cough, and fever, for instance, people may accidentally take more than the 4,000 mg daily limit without realizing it, increasing the risk of severe liver damage, said C. Michael White, a pharmacologist and pharmacist and chair of pharmacy practice at the University of Connecticut.

If you have cramps

Although either acetaminophen or ibuprofen can reduce pain from menstrual cramps, some research suggests that NSAIDs such as ibuprofen may provide slightly better pain relief because they reduce the production of prostaglandins, which trigger the uterine contractions that cause cramping.

If you have dental pain

Both medications can treat dental pain, but ibuprofen can help target inflammation or swelling associated with some dental issues.

Combining the two can be effective as well, particularly for more severe pain. A 2025 study found that a combination of acetaminophen and ibuprofen after dental surgery for impacted wisdom teeth provided better pain control than a prescription opioid combined with acetaminophen.

If you are pregnant

Ibuprofen is not recommended during pregnancy because NSAIDs have been linked to fetal complications, particularly later in pregnancy, Borucki said. Acetaminophen is generally considered the preferred first-line treatment for pain and fevers during pregnancy, according to the American College of Obstetricians and Gynecologists (ACOG).

Amid federal health concerns about Tylenol in pregnancy, the Food and Drug Administration announced last year that it was initiating the process for a label change “to reflect evidence suggesting that the use of acetaminophen by pregnant women may be associated with an increased risk of neurological conditions such as autism and ADHD in children.” The World Health Organization (WHO) stated, however, that there is no conclusive evidence confirming a possible link. And in separate statements, ACOG, the American Academy of Pediatrics, the American College of Medical Toxicology and the Society for Maternal-Fetal Medicine said acetaminophen remains appropriate for treating fever and pain during pregnancy when used as directed.

Avoiding the medication when it is needed to treat fever could lead to potential harm as “there is a significant risk with uncontrolled fever, both to the mother and to the fetus,” Gavrilescu said.

If you have certain health conditions or are taking certain medications

People who have liver disease, are heavy alcohol consumers, or taking certain medications that affect liver function should consult their doctor before taking acetaminophen. As we mentioned, exceeding the maximum daily dose of 4,000 mg can lead to severe liver damage, including liver failure.

In people with high blood pressure, a history of heart attack or stroke or heart failure, NSAIDs such as ibuprofen can increase the risk of serious cardiovascular events. NSAIDs can also raise the risk of gastrointestinal complications, including bleeding, especially in people with a history of stomach ulcers. And because they can reduce blood flow to the kidneys, people with kidney disease should consult a doctor before taking ibuprofen, White said.

Ibuprofen can interact with certain medications, as well. It can increase bleeding risk when taken with blood thinners such as warfarin, and it can interfere with some blood pressure medications, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta blockers and diuretics, potentially making them less effective, White said.

Although both acetaminophen and ibuprofen “can be very helpful, use them judiciously. And when you’re able to come off of them, definitely wean yourself off of them,” Borucki said.