BACKGROUND Optimal blood loss control measures during myomectomy remains a challenge in surgical management of uterine leiomyomas. Careful patient selection and the use of peri-cervical tourniquet are the two promising methods that are commonly employed. Intra-myometrial injection of vasopressin during myomectomy is another method that could minimise of blood loss during myomectomy. However, there is paucity of knowledge to guide its use in myomectomy. OBJECTIVE To assess the efficacy of intra-myometrial vasopressin by determining whether it is noninferior to (as good as) a placebo in reducing intra-operative blood loss during abdominal myomectomy after application of peri-cervical Foley’s catheter in both instances. METHODS This was a randomized, double-blind non-inferiority trial. One hundred and twenty-eight patients with uterine leiomyoma of 14 – 30 weeks size were recruited from the gynecology clinic, after obtaining their informed consent. They were randomized to either receive 20 IU (1ml) of vasopressin in 19mls of normal saline or 20ml of normal saline at the planned uterine incision site during myomectomy after traditional tourniquet application. Myomectomy was then performed in line with departmental protocol. The efficacy of vasopressin was assessed by a primary outcome,estimated intra-operative blood loss, and two secondary outcomes, post-operative hematocrit and the need for blood transfusion.P-value < 0.05 was considered statistically significant at 95% confident level.