The rate of bleeding complications after major orthopedic surgery approximates 2%. It is unclear whether a systematic switch of routine thromboprophylaxis has an impact on the rate of postoperative bleeding complications. We analyzed prospectively recorded postoperative bleeding complications and symptomatic venous thromboembolic events in 8,176 consecutive orthopedic patients at the Schulthess Clinic Zurich during a systematic switch of thromboprophylaxis from nadroparin to enoxaparin in the year 2004. Overall, 3,893 patients received nadroparin in the first nine-month observation period before the switch and 4,283 patients received enoxaparin in the second nine-month observation period after the switch. Overall, 96 (2.5%) patients in the first period and 70 (1.6%) patients in the second period suffered a postoperative bleeding complication requiring surgical revision, puncture, or transfusion (p < 0.01). Five objectively confirmed symptomatic venous thromboembolic events during hospitalization in the first period and three events in the second period were recorded. In conclusion, the switch of thromboprophylaxis in a large orthopedic clinic did not cause an increase of postoperative bleeding complications and therefore was accompanied by high patient safety.