Bleeding is the major complication associated with warfarin therapy. Some antidepressants are also associated with increased bleeding risk. Warfarin and antidepressants are used frequently in combination, but it is unclear whether concomitant use increases the risk of bleeding beyond that with warfarin alone. The primary goal of this study was to determine whether the use of warfarin and an antidepressant increases the risk for bleeding outcomes compared with the use of warfarin alone. The secondary goal was to characterize the risk of bleeding in warfarin-treated patients taking one specific class of antidepressant, selective serotonin reuptake inhibitors (SSRIs).