BACKGROUND: Postsurgical venous thromboembolism remains a leading cause of hospital morbidity. Data to support venous thromboembolism prophylaxis guidelines in lower extremity flap surgery are lacking. The purpose of this study was to explore the effect of pedicled lower extremity flap harvest on venous thromboembolism development in the setting of abdominal or perineal reconstruction. METHODS: One hundred twenty-six patients undergoing unilateral lower extremity flap harvest for abdominal or perineal reconstruction were included. The contralateral leg served as an internal control. Sixty comorbidity-matched patients who underwent abdominal/perineal resection without flap reconstruction provided an external control. Bivariate analyses included chi-square and t tests; logistic regression adjusted for confounding variables on venous thromboembolism development. RESULTS: All patients underwent flap reconstruction for an oncologic defect of the abdomen or perineum, with 80 percent undergoing perineal reconstruction. Most patients underwent anterolateral thigh (41 percent) or gracilis flap (40 percent) harvest. Eleven patients developed deep venous thromboses in one or more legs (9 percent): 10 of 11 (90.9 percent) in the donor extremity and five (45.5 percent) contralaterally (p = 0.022). Patients who underwent flap harvest had a 10-fold higher odds of venous thromboembolism formation when compared to comorbidity-matched controls without flap reconstruction (OR, 10.64; 95 percent CI, 1.11 to 102.34; p = 0.041). CONCLUSIONS: The rate of venous thromboembolism is higher than previously appreciated for reconstructive procedures of the abdomen and/or perineum that use pedicled lower extremity flaps-particularly in the operative extremity. Additional research can clarify the role for further prophylaxis or screening. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.