Objective To report a comparative analysis of laparoscopic simple prostatectomy (LSP) vs robot-assisted simple prostatectomy (RASP). Patients and Methods Consecutive cases of LSP and RASP done between 2003 and 2014 at 3 participating institutions were included in this retrospective analysis. The effectiveness of the two procedures was determined by performing a paired analysis of main functional and surgical outcomes. A multivariate analysis was also conducted to determine the factors predictive of "trifecta" outcome (combination of International Prostate Symptom Score <8, Qmax > 15 mL/second, and no perioperative complications). Results A total of 319 patients underwent minimally invasive simple prostatectomy at the participating institutions over the study period. Total prostate volume was larger in the RASP group (median 118.5 mL vs 109 mL, P =.02). Median estimated blood loss tended to be higher for LSP (300 mL vs 350 mL, P =.07). There was no difference in terms of catheterization time (P =.3) and hospital stay (P =.42). A higher rate of overall postoperative complications was recorded in the RASP group (17.7% vs 5.3%), but rate of major complications was not significantly different between the two techniques (2.3 vs 2.1, P =.6). Subjective and objective parameters significantly improved for both LSP and RASP. On multivariable analysis, only two factors were associated with likelihood of obtaining a favorable (trifecta) outcome: age (odds ratio: 0.94; P =.03) and body mass index (odds ratio: 0.84; P =.03). Conclusion Both LSP and RASP can be regarded as safe and effective minimally invasive surgical treatments for bladder outlet obstruction due to large prostate glands.