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Which painkiller is best for migraine? The Best OTC Pain Reliever For Whatever Hurts Acetaminophen (Tylenol) Acetaminophen is best known for relieving headaches, minor aches and pains, and reducing fever. Ibuprofen (Advil/Motrin) And Naproxen (Aleve) Take: Ibuprofen Or Naproxen. Take: Acetaminophen. Take: Ibuprofen Or Naproxen. Take: Acetaminophen Or Aspirin.