PURPOSE: Performance of a skin-sparing mastectomy with immediate reconstruction provides psychological satisfaction and good cosmetic outcome for patients with breast cancer. However, this is a lengthy procedure to perform, and there is increased risk of pulmonary thromboembolism (PTE). The purpose of this study was to evaluate the efficiency of the use of low molecular weight heparins (enoxaparin) for prophylaxis against a pulmomary thromboembolism followed by mastectomy with an immediate transverse rectus abdominis myocutaneous flap (TRAM) in breast cancer. METHODS: A total of 123 patients underwent a skin-sparing mastectomy with an immediate TRAM. The "non-enoxaparin group" wore compression stockings for PTE prophylaxis and the "enoxaparin group" received enoxaparin (40 mg SC injection, once daily starting 2 hr before surgery and continuing for 6 days postoperatively) in conjunction with the use of compression stockings. Lung perfusion, inhalation scans, and serum D-dimer assays were performed on postoperative day 3. If findings were clinically suspicious or intermediate to high probability of a PTE in a lungs scan, embolism computed tomography was performed. Patients were prospectively investigated according to the clinicopathological data. We compared the incidence of PTE and hemorrhagic complications between the two groups. RESULTS: There were no significant clinicopathological differences between the two groups. Eleven patients developed a PTE (nine patients in the non-enoxaparin group and two patients in the enoxaparin group). The prevalence rate of a PTE was 17.3% and 3.2% for each group, respectively (p=0.01). One patient in the non-enoxaparin group required a second operation for bleeding control and three patients in the enoxaparin group needed transfusions. There were minor hemorrhagic complications in the enoxaparin group that improved after supportive management. CONCLUSION: Although there were minor hemorrhagic complications, enoxaparin is safe and effective in a preventing PTE in patients that undergo immediate reconstruction after a skin-sparing mastectomy.