Objective: Laparoendoscopic single-site surgery (LESS) is increasingly popular in urology. However, data on LESS radical cystectomy (LESS-RC) are immature, and no adequate comparative study has assessed conventional laparoscopic radical cystectomy (CL-RC) vs LESS-RC. The primary aim of this study was to compare efficiency and safety of LESS-RC and CL-RC for patients with bladder urothelial carcinoma (BUC). Materials and Methods: A retrospective and case-matched control comparative analysis was performed of patients who underwent LESS-RC (n=54) and CL-RC (n=108) from January 2011 to June 2015. Oncologic, complication and perioperative outcomes were collected and evaluated. Results: LESS-RC vs CL-RC was associated with less estimated blood loss (EBL; median, 270 vs 337.5mL; p=0.014), postoperative pain (median, 4.0 vs 6.0 scores; p=0.001), and shorter convalescence (time to ambulation and oral intake, median, 2.5 vs 3 days; p=0.002 and 5 vs 6 days; p=0.004, respectively). No significant differences were noted for LESS-RC and CL-RC regarding the lymph node yield (median: 18 vs 20; p=0.101). Median follow-up time was 33.5 months (interquartile range [IQR]: 23-41.3 months) and 33 months (IQR: 23-43 months) for the LESS-RC and CL-RC groups, respectively. No significant differences were noted for LESS-RC and CL-RC regarding estimated 24-month overall survival (86.7% vs 88.1%, p=0.703), cancer-specific survival (88.3% vs 90.9%, p=0.539), and recurrence-free survival (80.2% vs 87.5%, p=0.619), even when substratified according to tumor stage (pT(3) or higher) and lymph node status (pN+). Early, late, and 90-day overall complication rates were similar. In multivariate analyses, LESS-RC was not associated with recurrence and worse survival rates, but was associated with 90-day overall complications. Conclusions: This study demonstrated that LESS-RC and CL-RC have comparable efficiency and safety for patients with BUC. Compared to CL-RC, LESS-RC was with less postoperative pain, lower EBL, and more rapid convalescence, but was associated with 90-day overall complications.