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STUDY OBJECTIVE To evaluate if the addition of pharmacologic prophylaxis to mechanical prophylaxis for venous thromboembolism (VTE) is associated with change in perioperative outcomes in hysterectomy for benign indications. DESIGN Retrospective cohort study Setting: Michigan Surgical Quality Collaborative (MSQC) database Patients: Those who underwent hysterectomy between July 2012 and June 2015 when VTE prophylaxis data was collected. INTERVENTIONS Patients who received mechanical prophylaxis alone were compared to those receiving dual prophylaxis (mechanical and pharmacologic). Minimally invasive surgery (MIS) included laparoscopic, vaginal, robotic-assisted, and laparoscopic-assisted vaginal hysterectomy and were analyzed separately from abdominal (ABD) hysterectomy. MEASUREMENTS AND MAIN RESULTS Propensity score matching was used to minimize confounding due to differences in demographic and perioperative characteristics. The primary outcome was estimated blood loss (EBL). Secondary outcomes were operative time, postoperative blood transfusion, VTE, surgical site infection, reoperation, readmission, and death. There were 1,803 matched pairs in the MIS analysis. In the ABD analysis, 2:1 matching was used with a total of 1,168 patients receiving mechanical prophylaxis alone matched to 616 receiving dual prophylaxis. EBL was higher by 54.5 cc (95% CI, 16.9 - 92.1) in those receiving dual prophylaxis in the ABD analysis but did not differ between groups in the MIS analysis. Operative time was significantly longer with dual prophylaxis in both MIS (18.3 mins; 95% CI, 13.8 - 22.8) and ABD (15.3 mins; 95% CI 9.0 - 21.6) surgical approaches. There were no differences in other secondary outcomes. CONCLUSION The addition of pharmacologic prophylaxis to mechanical prophylaxis in benign hysterectomy was associated with longer operative time regardless of surgical approach and increased EBL in ABD hysterectomy. Given very low rates of VTE, no difference in other perioperative outcomes, and possible harm, it seems reasonable to encourage individualized rather than routine use of pharmacologic prophylaxis in benign hysterectomy patients receiving mechanical prophylaxis.