Purpose Open simple prostatectomy (OSP) is a standard surgical technique for patients with benign prostatic hyperplasia with prostate size larger than 80 ml. As a minimally invasive approach, robot-assisted simple prostatectomy (RASP) emerged as a feasible surgical alternative. Currently, there are no definite recommendations for the standard use of RASP. Therefore, we aimed at investigating various clinical outcomes comparing RASP with OSP. Methods In this retrospective single-center study, we evaluated clinical data from 103 RASP and 31 OSP patients. Both cohorts were compared regarding different clinical characteristics with and without propensity score matching. To detect independent predictive factors for clinical outcomes, multivariate logistic regression analysis was performed. Results Robot-assisted simple prostatectomy patients demonstrated a lower estimated blood loss and need for postoperative blood transfusions as well as less postoperative complications. OSP had a shorter operative time (125 min vs. 182 min) longer hospital stay (11 days vs. 9 days) and longer time to catheter removal (8 days vs. 6 days). In the multivariate analysis, RASP was identified as an independent predictor for longer operative time, lower estimated blood loss, shorter length of hospital stay, shorter time to catheter removal, less postoperative complications and blood transfusions. Conclusion Robot-assisted simple prostatectomy is a safe alternative to OSP with less perioperative and postoperative morbidity. Whether OSP (shorter operative time) or RASP (shorter length of hospital stay) has a more favorable economic impact depends on the particular conditions of different health care systems. Further prospective comparative research is warranted to define the value of RASP in the current surgical management of benign prostatic hyperplasia.