ObjectiveTo compare the efficacy and safety of intramyometrial vasopressin plus rectal misoprostol with intramyometrial vasopressin alone to reduce blood loss during laparoscopic myomectomy. Study designA randomized, single-blind, controlled trial was conducted at All India Institute of Medical Sciences, New Delhi, India. Sixty women with symptomatic leiomyoma scheduled for laparoscopic myomectomy were recruited for the study. Thirty women received intramyometrial vasopressin plus rectal misoprostol (30 min before procedure) (Group I) and 30 women received intramyometrial vasopressin alone (Group II) during laparoscopic myomectomy. The primary outcome measure was intra-operative blood loss during surgery. Secondary outcome measures included decrease in postoperative haemoglobin, ease of enucleation of myomas, duration of surgery, need for additional haemostatic measures or blood transfusion, intra- and postoperative morbidity, and duration of hospital stay. ResultsThe baseline demographic features and characteristics of leiomyomas were comparable in both groups. The mean (±standard deviation) blood loss in Group I was 139 ± 96.7 ml, which was significantly less than that for Group II (206 ± 101.2 ml) (p = 0.008). The mean postoperative haemoglobin was 11.6 ± 1.3 g/dl in Group I and 10.0 ± 1.2 g/dl in Group II (p = 0.001). Although blood loss was not clinically significant in either group, the decrease in haemoglobin was significantly higher in Group II. The mean score for ease of enucleation (surgeon-rated measure) was significantly lower in Group I (2.6 ± 1.1) compared with Group II (3.4 ± 1.1) (p = 0.029). Intra- and postoperative vital signs, duration of surgery, need for blood transfusion and postoperative morbidity were comparable in both groups. ConclusionsThe addition of rectal misoprostol to intramyometrial vasopressin led to a significant reduction in blood loss and decreased the postoperative drop in haemoglobin. The combination also improved the ease of enucleation of myomas.