From 1957 to 1982, 115 patients underwent radical vulvectomy and bilateral inguinal lymphadenectomy for invasive squamous carcinoma of the vulva. From 1957 to 1971, 57 patients received perioperative prophylactic sodium warfarin (Coumadin) as prophylaxis against pulmonary embolism. From 1971 to 1976, 27 consecutive patients received dextran-40 as prophylaxis for pulmonary embolism and to improve the microcirculation to the inguinal skin flaps. Because of the report that dextran-40 is a cause of acute renal failure, this study was terminated and the subsequent 19 patients were treated with mini-dose heparin because of the reported benefit as prophylaxis against thromboembolic disease. During the 25-year period, 12 patients received no prophylactic anticoagulants. Mini-dose heparin resulted in a significant morbidity not previously reported in patients undergoing inguinal lymphadenectomy: 43% (8/19) of the mini-dose heparin patients, 7% (2/27) of the dextran-40 patients, 0% (0/57) of the sodium warfarin patients, and none of the 12 patients not receiving perioperative prophylaxis developed inguinal lymphocysts (P less than .001). There was no significant difference in the prevention of pulmonary embolism between the mini-dose heparin (0/19), dextran-40 (0/27), and no treatment groups (0/12) as compared to the 5% (3/57) incidence in the sodium warfarin patients (.10 less than P less than .50). The significant relationship between prophylactic heparin and the subsequent development of inguinal lymphocysts and the need to reassess its role in prevention of pulmonary embolism in patients undergoing lymphadenectomy is discussed.