Fish oil is used to lower triglycerides and for the secondary prevention of cardiovascular events in patients with coronary artery disease. Many of these patients will also be taking aspirin and clopidogrel. Any of these medications alone can increase the risk of bleeding; however, the risk of bleeding in patients taking all 3 of these medications has not been studied. We retrospectively reviewed the medical records for bleeding complications in 182 patients, most with coronary artery disease (mean age 61 +/- 11 years, 82% men) and being treated with high-dose fish oil (mean dose 3 +/- 1.25 g), aspirin (mean dose 161 +/- 115 mg), and clopidogrel (mean dose 75 mg), and in 182 age- and gender-matched controls treated with aspirin and clopidogrel alone. During a mean follow-up period of 33 months, 1 major bleeding episode occurred in the treatment group and no major bleeding episodes occurred in the control group (p = 1.0). During follow-up, 4 minor bleeding episodes (2.2%) occurred in the treatment group and 7 (3.9%) in the control group. More patients had minor bleeding complications in the control group than in the treatment group; however, the difference was not statistically significant (p = 0.5). In conclusion, high-dose fish oil is safe in combination with aspirin and clopidogrel and does not increase the risk of bleeding compared with that seen with aspirin and clopidogrel alone.