Acetaminophen vs. NSAIDs: Which Over-the-Counter Medicine Should I Use?

Pain medicine you buy at the store may be one of the first things you reach for when you hurt yourself, have a headache or backache, or feel discomfort due to some other nagging ailment that doesn’t require a visit to the doctor. Called “over-the-counter” or OTC treatments, you can get these medicines without a prescription, and they will ease the pain, bring down a fever, and treat inflammation, depending on which one you take.

But, like any drug, OTC pain medicines also have risks and potential side effects. And there can be health consequences if you take too much of them.

“Over-the-counter medicines can be very helpful, but people need to take them with caution,” says anesthesiologist Donna-Ann Thomas, MD, Yale Medicine’s division chief of pain medicine. “You have to remember you are still taking a medication. It’s important to follow the directions on the label, especially if you have medical issues or take other medications.”

Below, we answer common OTC medication questions.

Most OTC medications fall into one of two categories: nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, and there are different subtypes and brands (and generic options) within each of these categories.

What they are: These medicines, which include aspirin, ibuprofen, and naproxen, among other subtypes, relieve pain and reduce fever. They also treat inflammation and related symptoms, including swelling from arthritis, as well as sprains and strains. Their ability to reduce inflammation may make them more effective than acetaminophen (see below).

How they work: All NSAIDs work in the same way: They inhibit two cyclooxygenase (COX) enzymes from making chemicals called prostaglandins, which contribute to inflammation and the swelling and pain that comes with them.

Cautions: Non-aspirin NSAIDs carry an FDA warning that high doses taken for a long time can potentially cause a heart attack or stroke. If you have a chronic condition, such as kidney disease, or if you take a blood thinner medication, it’s important to talk to your doctor before taking a NSAID.

What else to know: They’re not as gentle on the stomach as acetaminophen.

What you should use it for: Pain, fever, and inflammation. Different NSAIDs (more on that below) may be used for other reasons or specific problems.

Aspirin

What it is: Aspirin is an NSAID that can reduce fever and ease mild-to-moderate pain. In some cases, it also is used for the prevention and care of some cardiovascular conditions (ask your doctor if this is appropriate for you). Aspirin also is a blood thinner that inhibits blood clot formation, which can cause heart attacks and strokes—although for some people, the benefits of using aspirin this way may not outweigh the risks.

Common brand names: Bayer™ and Bufferin™ are some examples.

Cautions: Aspirin puts children under 18 at risk for Reye’s syndrome, which causes brain and liver damage. Pregnant women should be aware that certain doses of aspirin could harm the fetus and cause problems with delivery if taken 20 weeks or later into a pregnancy, so a conversation with their doctor is in order before taking it. In addition, while aspirin helps many people, it can have a negative impact on a list of common health conditions, including high blood pressure.

What else to know: For years, many adults have taken low-dose aspirin to help prevent heart attacks. But in 2022, the U.S. Preventive Services Task Force (USPSTF) issued recommendations stating that adults 60 and older should not start an aspirin regimen for this purpose. It recommended that people 40 to 59 with an estimated 10% or greater 10-year cardiovascular risk talk to a medical provider for help in making an individual decision about an aspirin regimen.

The USPSTF recommendation is based on research suggesting the benefits of aspirin don’t always outweigh the potential harms, which can include a higher risk of bleeding in the brain, intestines, and stomach, especially as people get older.

What you should use it for: Fever reduction and mild-to-moderate pain relief from arthritis, headaches, muscle aches, menstrual periods, and toothaches. Aspirin may also be used to prevent heart attacks in people with angina or who have had a heart attack. It is also used to prevent the recurrence of ischemic strokes or mini-strokes.

Ibuprofen

What it is: Ibuprofen, another NSAID, can help with arthritis, backache, common cold, fever, menstrual periods, and other aches and pains.

Brand names: Advil™ and Motrin™ are some examples.

Cautions: If you are 75 or older, talk to your doctor about the risks and benefits of taking ibuprofen. Talk to your doctor or dentist if you are having surgery or have one of the conditions listed on the label. Exercise caution if you have phenylketonuria (PKU), an inherited condition that requires avoiding the sweetener aspartame, among other food products, since some ibuprofen products contain aspartame.

There are special concerns around the timing of taking ibuprofen for women who are pregnant or trying to become pregnant. Ibuprofen may harm the fetus and cause delivery problems if it is taken around 20 weeks or later during pregnancy.

What else to know: Ibuprofen has a label warning that non-aspirin NSAIDs could increase the risk of heart attack or stroke. The FDA issued the warning in 2005 and strengthened it in 2015 after an expert panel reviewed additional information about the risks.

What you should use it for: Arthritis, backache, common cold, fever, menstrual periods, and other aches and pains.

Naproxen

What it is: This NSAID medication is longer-lasting than other NSAIDs and acetaminophen—it is taken every 8 to 12 hours as needed, while the other OTC medicines are typically in the 4- to 6-hour range. Like other NSAIDs, naproxen brings down fevers and relieves pain from ailments ranging from arthritis and muscle aches to the common cold.

Brand names: Aleve™ is a common example.

Cautions: It’s recommended that adults 65 or older take naproxen at lower doses than other people and for shorter periods to increase effectiveness and avoid side effects. Regardless of age, you should talk to your doctor or dentist if you are having surgery or have one of the conditions listed on the label.

As with ibuprofen, there are special concerns around the timing of taking naproxen for women who are pregnant or trying to become pregnant. This medication may temporarily decrease fertility in women, and it could harm the fetus and cause problems with delivery if it is taken around 20 weeks into the pregnancy or later.

What you should use it for: Fever, mild pain from arthritis, backaches, common cold, headaches, muscle aches, menstrual periods, and toothaches.