Warfarin is frequently used for the prevention and treatment of thromboembolism, yet it is associated with numerous drug interactions. Regarding over-the-counter pain medications, the preferred analgesic for those patients who are taking warfarin is acetaminophen. There are, however, reports of elevation in the international normalized ratio (INR) in those patients taking concurrent warfarin and acetaminophen. For those practitioners who manage warfarin therapy, there is little guidance regarding management of the drug-drug interaction between warfarin and acetaminophen. This review seeks to evaluate the drug interaction between warfarin and acetaminophen and provides recommendations for concurrent use of these drugs.