Abstract The aim of this study is to compare between combined preoperative rectal misoprostol plus perivascular vasopressin and tourniquet to decrease blood loss during abdominal myomectomy. In this randomized study, 104 patients were randomly allocated to receive either combined 400 μg rectal misoprostol plus perivascular vasopressin (n = 52) or tourniquet (n =52). The main outcome measure was the operative blood loss. Secondary outcome measures included the requirement for blood transfusion, the change in hemoglobin level after operation, and incidence of complications. Blood loss was significantly greater in the group with tourniquet (375.7± 292.3 mL) than in the group with rectal misoprostol plus perivascular vasopressin (254.1± 185.4 mL) (P=0.03). The group with tourniquet had a significant decrease in Hb level 24 h after operation (P< 0.04). Blood transfusion rate was significantly greater in the group with tourniquet (P< 0.04). The febrile morbidity was comparable in the two groups. Rectal misoprostol plus perivascular vasopressin was found to be more effective than tourniquet for decreasing blood loss during abdominal myomectomy.