Purpose of investigation: We performed a randomized clinical trial to estimate whether preoperative use of misoprostol may reduce intraoperative blood loss of patients treated by minimally invasive surgery (MIS), such as laparoscopic (LM) or laparoscopically assisted myomectomy (LAM). Methods: Sixty-seven menstruating patients with three or less myomas of a maximum diameter of 90 mm, scheduled for MIS, were randomly allocated to receive a preoperative single dose of intravaginal misoprostol or placebo. Sixty-four patients remained in the final analysis: 30 in the misoprostol (I) and 34 in the placebo group (II). Estimated blood loss (EBL), decline of postoperative hemoglobin (Hb) and side-effects of administered agent were the outcomes of main interest. Results: The EBL was significantly higher in the placebo versus misoprostol group (217 ± 74 vs 126 ± 41, respectively). Similarly, the decline of postoperative Hb was significantly higher in group II (1.6 ± 0.43) compared to group I (1 ± 0.33). The operative time was comparable in both groups, while the rate of side-effects was similar between groups. Conclusion: The preoperative use of misoprostol in patients with uterine fibroids managed by minimally invasive surgery significantly reduces intraoperative blood loss. Misoprostol might be useful for the prevention of postoperative anemia in more extended minimal invasive interventions, such as myomectomy of large fibroids or laparoscopic hysterectomy.;">