Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization, but there is a paucity of evidence to guide the use of post-discharge prophylaxis (PDP). A retrospective cohort study of trauma patients deemed moderate-to-high risk for VTE (risk assessment profile score RAP ≥5) who were prescribed PDP based on an internal clinical guideline assessing injury pattern and mobility status. PDP patients were compared with those that did not receive post-discharge prophylaxis (NPDP). 1512 patients were included. PDP group had higher mean RAP score (7.3 vs. 6.4, p ​< ​0.001), more likely to have a complex orthopedic fracture and underwent a longer median hospital (4.7 vs. 2.9 days, p ​< ​0.001). No difference between groups in 90-day VTE (11 1.5 ​% (PDP) vs. 8 1.0 ​% (NPDP), p ​= ​0.50), clinically relevant bleeding (p ​= ​0.58), or readmission (p ​= ​0.46). VTE incidence, clinically relevant bleeding, and readmission 90-days after hospital discharge were low and similar between PDP and NPDP groups. PDP prescribed in a presumably higher VTE risk trauma population may mitigate the long-term risk of VTE. •Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization.•Patients who received post-discharge prophylaxis (PDP) were at higher risk of VTE.•Incidence of 90-day post-discharge VTE, clinically relevant bleeding, and readmission were similar between groups suggesting mitigation of VTE in high risk trauma patients.