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Abstract Background Thoracentesis is a low-risk procedure for bleeding (approx. 2%). Data regarding safety of thoracentesis under treatment with clopidogrel is scarce, and current guidelines are not evidence based. We performed a retrospective study to evaluate the rate of bleeding complications of thoracentesis under clopidogrel in hospitalized patients. Methods Retrospective chart review of hospitalized patients undergoing thoracentesis with or without clopidogrel treatment. Demographic and clinical data, diagnostic ICD9 codes, and use of ultrasound were extracted. Bleeding endpoints were defined as hemothorax, drop of > 2 g/dL hemoglobin, or need for packed red cell transfusion. Results The study group comprised of 88 cases and 169 controls. Four bleeding complications were noted in the cases group, versus 5 in the control group (RR 1.53, 95% CI 0.4–5.5). Conclusion Thoracentesis may be performed safely in patients receiving clopidogrel. Bleeding event rates are consistent with previous reports of thoracentesis in general.