Background Prophylactic anticoagulation is routinely used in the inpatient setting; however, the risk of venous thromboembolism (VTE) remains elevated after discharge. Extensive evidence and clinical guidelines suggest post-discharge VTE prophylaxis is critical in at-risk populations, but it remains severely underused in practice. Study Design We performed a single-institution retrospective, nonrandomized, pre- and post-intervention analysis of a systematic post-discharge pharmacologic prophylaxis program against the primary end point, which is post-discharge symptomatic VTE. An institutional American College of Surgeons NSQIP dataset was used to identify patients and outcomes. Patients undergoing major abdominal surgery for malignancy or inflammatory bowel disease were eligible for the post-discharge VTE prevention program. Results Among 1,043 patients who underwent abdominal surgery for malignancy or inflammatory bowel disease, 800 (77%) were in the pre-intervention cohort and 243 (23%) patients were in the post-intervention cohort. Rates of inpatient VTE did not significantly differ between cohorts (0.7%, n = 6 pre-intervention vs 1.7%, n = 4 post-intervention; p = 0.25). However, compared with the pre-intervention cohort, patients in the post-intervention cohort demonstrated a significantly lower post-discharge VTE rate (2.5%, n = 20 pre-intervention vs 0.0%, n = 0 post-intervention; p < 0.01). Conclusions A systematic post-discharge VTE prophylaxis program including provider education, local guideline adaptation, bedside medication delivery, and education for at-risk patients, was associated with significantly fewer post-discharge VTE events. © 2016 American College of Surgeons