Background: To extend the benefits of minimally invasive surgery, an increasing enthusiasm has emerged for the laparo-endoscopic single-site surgery (LESS). The idea of LESS is to allow inserting multiple laparoscopic instruments through only one umbilical incision instead of multiple abdominal incisions. Methods: Sixty patients from three different centers in Germany were randomized (1:1) to conventional laparoscopic hysterectomy (n = 31) or LESS hysterectomy (n = 29). The study focused in particular on the safety and efficacy of both techniques. Results: The mean operative time was comparable in both groups (68.2 vs 73.6 min., p = 0.409; 95% CI − 18.69-7.12). No differences were seen regarding estimated blood loss (p = 0.915; 95% CI − 21.02-18.88), intra-and postoperative complications (p = 0.944), and wound infection rates (p = 0.944). Patients within the LESS group experienced significantly less pain in the first 24 h postoperatively (p = 0.006); the pain scores at 3, 5, 7 days and 2 months postoperatively were comparable. Conclusion: LESS hysterectomy is a reliable and safe option in gynecologic surgery. Compared to conventional laparoscopic hysterectomy, LESS surgery demonstrated comparable surgical properties in regard to blood loss, duration of surgery, and intra-/postoperative complications. Notably, patients undergoing LESS hysterectomy experienced some less pain postoperatively.