BACKGROUND: Heparin is commonly used for venous thromboembolism prophylaxis; however, the incidence of acquired thrombocytopenia in this setting has not been well described. METHODS: The Complications After Thrombocytopenia Caused by Heparin (CATCH) Registry was designed to evaluate the risk of thrombocytopenia among patients receiving heparin in diverse clinical settings. We examined the incidence, management, and outcomes of thrombocytopenia (platelet count decrease ≥50% or to nadir <150×10(9)/L) among patients with normal admission platelet counts (≥150×10(9)/L) who received ≥72 hours of heparin venous thromboembolism prophylaxis. RESULTS: Among 1017 patients receiving heparin venous thromboembolism prophylaxis, 190 (19%) developed thrombocytopenia. Factors significantly associated with the development of thrombocytopenia include higher admission platelet count, ventilator use, prolonged heparin exposure, unfractionated heparin use, lower admission blood pressure, and cardiac surgery. For thrombocytopenic patients, only 5% received serologic testing for heparin-induced thrombocytopenia, and a hematology consult was obtained in 3%, but none were switched to a direct thrombin inhibitor. Acquired thrombocytopenia was not associated with increased in-hospital risk of mortality or thromboembolic events (adjusted odds ratio 1.06; 95% confidence interval, 0.57-1.95); however, it was associated with increased Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk (adjusted odds ratio 4.49; 95% confidence interval, 2.24-9.02). CONCLUSION: Thrombocytopenia occurs frequently in patients on heparin venous thromboembolism prophylaxis, yet its diagnosis has minimal impact on downstream management. The development of thrombocytopenia is associated with increased bleeding risk.