Background: Post-surgical venous thromboembolism (VTE) remains a common and costly complication that is associated with significant morbidity and mortality. Immediate and delayed free-flap breast reconstruction involves major risk factors for this potentially preventable complication. The objective of this study was to clarify the incidence of symptomatic and asymptomatic VTE in the free-flap breast reconstruction population receiving post-operative thromboprophylaxis.Methods: A prospective cohort study of 100 consecutive patients who underwent autologous free-flap breast reconstruction at a single cancer center was conducted. The post-operative thromboprophylaxis regimen, based on the American College of Chest Physicians (ACCP) guidelines, consisted of in-hospital low-molecular weight heparin (LMWH), perioperative sequential compression devices (SCD) and early ambulation. All patients systematically underwent a bilateral lower extremity duplex ultrasound (US) before discharge to objectively assess the status of the lower extremity deep venous system. Results: From June 2007 to March 2009, there were 117 free-TRAM and DIEP flaps for breast reconstruction. Of these, 100 patients underwent post-operative bilateral lower extremity duplex ultrasound before discharge. The incidence of postoperative deep venous thrombosis (DVT) confirmed by duplex US was 2%, all events being clinically silent calf venous thrombosis of the posterior tibial vein. Of these, one DVT was categorized as chronic since the venous system contained partially compressible echogenic material. There were no reported pulmonary embolus and no sudden death consequently to VTE. Complications associated with the use of LMWH were rare, with a 1.7% incidence of reoperative hematoma. Conclusion: The data from this prospective cohort study demonstrates that the incidence of DVT in breast reconstruction patients receiving post-operative prophylaxis is low. Of note, none of the deep venous thrombosis diagnosed in this study were clinically overt, and neither involved major deep venous systems such as the femoral or iliac vessels. There were no reported pulmonary embolism or sudden death associated with VTE. In addition, the use of LMWH did not significantly increase the rate of reoperative hematomas. A combined post-operative thromboprophylaxis regimen consisting of in-hospital LMWH, perioperative SCDs and early ambulation is safe and efficient in preventing VTE in the post-mastectomy patient population undergoing immediate or delayed free-flap breast reconstruction.