To compare perioperative outcomes and postoperative pain of minilaparoscopic (M-LPS) and laparoendoscopic single-site total hysterectomy (LESS).Prospectively randomized study (Canadian Task Force classification II-2).Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome.A total of 86 patients underwent total hysterectomy. Seventy-one met the inclusion criteria and were included in this study. Three of them refused randomization, 34 were randomly assigned to undergo to single-port hysterectomy and 34 to undergo to minilaparoscopy.The operative technique is the same in the 2 groups with the exception of videolaparoscopy, port type, and some specific instruments. All surgical procedures were performed with an intrauterine manipulator. Single-port hysterectomy was performed through a multichannel single trocar inserted in the umbilicus. Minilaparoscopic hysterectomy was performed through one optical transumbilical 5-mm trocar and three 3-mm suprapubic ancillary ports.Sixty-eight patients met the inclusion criteria and were enrolled in the study. The baseline characteristics of the 2 groups were comparable. Median operative time was longer in LESS with respect to M-LPS (120 minutes vs 90 minutes; p = .038). There were no differences between the 2 groups for median estimated blood loss, ileus, and postoperative stay. Additional 5-mm port insertion was needed in 1 case (2.9%) in the M-LPS group and in 2 cases (5.9%) in the LESS group, respectively (p = .311). No patient had development of intraoperative or early postoperative complications. Patients in the M-LPS group experienced a minor pain at each evaluation, compared with patients who underwent LESS. The rescue analgesic requirement was similar in the 2 groups.Laparoscopic hysterectomy can be safely performed by M-LPS and LESS. M-LPS is associated with significantly lower operative time and less postoperative pain than LESS. Advantages of M-LPS hysterectomy than LESS have no noteworthy impact on the patients' early postoperative management. The decision on the best access to the hysterectomy might take into account the surgeon's skill and feeling with the different possible approaches.