The risk of venous thromboembolism (VTE) for patients taking an antiplatelet agent is largely unknown. This study aimed to investigate the association between antiplatelet agent use before admission with the risk of in-hospital VTE in surgical intensive care unit (ICU) patients. A retrospective review of all patients admitted to the surgical ICU at a Level I trauma center over 30 months was performed. Patients who underwent diagnostic imaging for VTE were selected. Patients were divided based on whether or not antiplatelet agents were used before admission (APTA vs NAPTA). The primary outcome was VTE occurrence. A forward logistic regression model was used to identify factors independently associated with the primary outcome. During the study period, 461 (24%) patients met inclusion criteria: 70 (15%) APTA and 391 (85%) NAPTA. After adjusting for confounding factors, APTA patients were at a significantly higher risk for developing VTE (59 vs 40%; adjusted odds ratio, 1.8; 95% confidence interval, 1.0 to 3.0; adjusted P = 0.04). Whether or not antiplatelet agents were resumed during the hospital stay and the day on which they were resumed did not affect VTE risk. In conclusion, surgical ICU patients receiving antiplatelet agents before admission are at a significantly higher risk for development of VTE.