OBJECTIVE To evaluate the safety of preoperative enoxaparin in patients undergoing major gynecologic oncology surgery. METHODS We identified a retrospective cohort group of patients undergoing major gynecologic oncology surgery from June 2002 to June 2004. Exclusion criteria included laparoscopic surgery, inferior vena cava filter, history of venous thromboembolism, and current anticoagulation for prior venous thromboembolism. All patients received prophylaxis with sequential pneumatic compression devices and early ambulation. We identified patients who received (preoperative and postoperative) enoxaparin (20-40 mg) and compared them to patients who received no additional prophylaxis other than pneumatic compression alone. Patient outcomes including estimated blood loss, blood transfusions, operative time, and length of hospital stay were collected. Statistical analysis was performed using the χ Wilcoxon rank sum tests. This study was approved by the institutional review board. RESULTS We identified 122 patients who met our study criteria; there were 63 patients who received preoperative enoxaparin and 59 patients who received no additional prophylaxis. Both groups were similar in age, body mass index, race, comorbidities, cancer diagnosis, and surgical procedure. There was no significant difference between the enoxaparin group and the sequential pneumatic compression devices-only group regarding transfusion rates (29% and 27%; P = 0.86), operating time (150 and 140 minutes; P = 0.16), blood loss greater than 500 cc (35% and 37%; P = 0.79), and length of stay (5 vs 6 days). CONCLUSION The use of preoperative enoxaparin is not associated with increased blood loss, transfusion requirements, operative time, or hospital stay among patients having major gynecologic surgery.