Warfarin, sold under the brand name Coumadin among others, is used as an anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who have atrial fibrillation, valvular heart disease, or artificial heart valves. Warfarin may sometimes be prescribed following a ST-segment elevation myocardial infarction and orthopedic surgery. It is usually taken by mouth, but may also be administered intravenously.

The common side effect, a natural consequence of reduced clotting, is bleeding. Less common side effects may include areas of tissue damage, and purple toes syndrome. Use is not recommended during pregnancy. The effects of warfarin are typically monitored by checking prothrombin time (INR) every one to four weeks. Many other medications and dietary factors can interact with warfarin, either increasing or decreasing its effectiveness. The effects of warfarin may be reversed with phytomenadione (vitamin K₁), fresh frozen plasma, or prothrombin complex concentrate.

Warfarin decreases blood clotting by blocking vitamin K epoxide reductase, an enzyme that reactivates vitamin K₁. Without sufficient active vitamin K₁, the plasma concentrations of clotting factors II, VII, IX, and X are reduced and thus have decreased clotting ability. The anticlotting protein C and protein S are also inhibited, but to a lesser degree. It is wrongly described as a "vitamin K antagonist". This term is incorrect. Warfarin does not antagonize the action of vitamin K1, but rather antagonizes vitamin K1 recycling, depleting active vitamin K1. A few days are required for full effect to occur, and these effects can last for up to five days. Because the mechanism involves enzymes such as VKORC1, patients on warfarin with polymorphisms of the enzymes may require adjustments in therapy if the genetic variant that they have is more readily inhibited by warfarin, thus requiring lower doses.

Warfarin first came into large-scale commercial use in 1948 as a rat poison. It was formally approved as a medication to treat blood clots in humans by the U.S. Food and Drug Administration in 1954. In 1955, warfarin's reputation as a safe and acceptable treatment for coronary artery disease, arterial plaques, and ischemic strokes was bolstered when President Dwight D. Eisenhower was treated with warfarin following a highly publicized heart attack. It is on the World Health Organization's List of Essential Medicines. Warfarin is available as a generic medication and is sold under many brand names. In 2023, it was the 116th most commonly prescribed medication in the United States, with more than 5 million prescriptions.

Warfarin is indicated for the prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism; prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement; and reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Warfarin is used to decrease the tendency for thrombosis, or as secondary prophylaxis (prevention of further episodes) in those individuals who have already formed a blood clot (thrombus). Warfarin treatment can help prevent formation of future blood clots and help reduce the risk of embolism (migration of a thrombus to a spot where it blocks blood supply to a vital organ).

Warfarin is best suited for anticoagulation (clot formation inhibition) in areas of slowly running blood (such as in veins and the pooled blood behind artificial and natural valves), and in blood pooled in dysfunctional cardiac atria. Thus, common clinical indications for warfarin use are atrial fibrillation, the presence of artificial heart valves, deep venous thrombosis, and pulmonary embolism (where the embolized clots first form in veins). Warfarin is also used in antiphospholipid syndrome. It has been used occasionally after heart attacks (myocardial infarctions), but is far less effective at preventing new thromboses in coronary arteries. Prevention of clotting in arteries is usually undertaken with antiplatelet drugs, which act by a different mechanism from warfarin (which normally has no effect on platelet function). It can be used to treat people following ischemic strokes due to atrial fibrillation, though direct oral anticoagulants (DOACs) may offer greater benefits.

Dosing of warfarin is complicated because it is known to interact with many commonly used medications and certain foods. These interactions may enhance or reduce warfarin's anticoagulation effect. To optimize the therapeutic effect without risking dangerous side effects such as bleeding, close monitoring of the degree of anticoagulation is required by a blood test measuring an prothrombin time (INR). During the initial stage of treatment, INR is checked daily; intervals between tests can be lengthened if the patient manages stable therapeutic INR levels on an unchanged warfarin dose. Newer point-of-care testing is available and has increased the ease of INR testing in the outpatient setting. Instead of a blood draw, the point-of-care test involves a simple finger prick.