Minimizing the number of port incisions during minimally invasive surgery is associated with improved outcomes and patient satisfaction. We designed this work to study the perioperative outcomes of robotic single-site myomectomy (RSSM) in comparison to robotic multiport myomectomy (RMM) in a certain subset of patients. The design of the study is a multicenter retrospective analysis (Canadian Task Force classification III). The setting was three university hospitals. Eighty patients with symptomatic uterine fibroids undergoing robot-assisted single-site myomectomy were selected for the study. These 80 consecutive RSSM patients were matched at the uterine fibroid tumor burden level with 95 consecutive RMM patients performed at the same institutions, by the same surgeons, within a similar time frame. The main outcome measures were estimated blood loss (EBL), operative time, overnight admission, and post-operative complications. Of the 175 women, 95 (54.2%) underwent RMM and 80 (45.7%) underwent RSSM. Single-site vs. multiport patient demographics differed significantly in mean age (39.1 vs. 35.6, p < 0.001), and BMI (25.3 vs. 27.5, p < 0.04). Pre-operative MRI fibroid characteristics were matched between the two cohorts. Fibroid size on imaging (5.8 cm vs. 5.9 cm, p = 0.4) and the number of fibroids removed (2.5 vs. 2.3, p = 0.08) were similar between the two groups. After adjustment for multiple covariates with regression models, single-site myomectomy and multiport myomectomy has comparable EBL (83.3 mL vs. 109.2 mL, p = 0.34), operative time (162.4 min vs. 162.4 min, p = 0.99), overnight admission (OR = 1.54, p = 0.44) and a post-operative complication (OR = 1.3, p = 0.78). In selected patients, robotic single-site myomectomy is equivalent to its multiport counterpart. Both surgical approaches are associated with low rates of intra-operative and post-operative complications.