Background: Venous thromboembolism (VTE) is a significant risk for women with gynecologic cancer. As the risk of VTE is increased along with morbidity and mortality in the gynecologic oncologic population undergoing major surgery, the focus of prophylaxis has shifted to also providing pre-operative prophylactic anticoagulation. Yet, there remains controversy in the optimal prophylactic regimen for the major surgical gynecologic cancer patient. The objective of this study was to define the incidence of VTE in gynecologic cancer patients prior to and after the institutional implementation of pre-operative heparin in the VTE prophylaxis regimen. Methods: A retrospective cohort study was performed in patients with gynecologic cancer who underwent a major surgical procedure from January 2010 to December 2016 at a single institution. The incidence of post-operative VTE was compared between patients who received post-operative mechanical and chemical prophylaxis and those who received a single dose of pre-operative heparin in addition starting in 2015. Factors including estimated surgical blood loss, amount and location of disease at time of surgery, and route of surgery were examined in those diagnosed with a VTE post-operatively. Results: Of the 609 surgical patients with gynecologic cancer prior to the initiation of a single dose of preoperative heparin, 42 (6.90%) were diagnosed with a post-operative VTE. After initiation of pre-operative heparin, 17 (3.27%) of 520 patients experienced VTE postoperatively. There was a significant difference between the incidence of VTE after the practice change (p < 0.006, 95% CI 1.03-6.23%). Surgical blood loss was similar in both groups. Those diagnosed with a VTE tended to have a heavy burden of disease at time of surgery and underwent laparotomy. Conclusions: A significant decrease in the incidence of VTE in patients with gynecologic malignancy undergoing surgery was seen with the initiation of a single dose of pre-operative heparin. This shift in the standard of care has had a meaningful impact at an institutional level and has potential to be impactful at a national level.