INTRODUCTION: Radical cystectomy represents the standard of care for localized muscle invasive or high-grade non-muscle invasive BCG unresponsive bladder cancer. Several randomized control trials have been published comparing open (ORC) with robot-assisted radical cystectomy (RARC). We aimed to summarize evidence in this setting with a systematic review and meta-analysis. EVIDENCE ACQUISITION: All published randomized prospective trials that compared ORC with RARC were retrieved through a systematic search according to PRISMA guidelines. Outcomes investigated were the risks of overall complications, high grade (Clavien-Dindo ≥3) complications, positive surgical margins, the number of lymph nodes removed, estimated blood loss, operative time, length of hospital stay, quality of life, overall survival (OS) and progression-free survival. A random effect model was applied. Subgroup analysis on the basis of the urinary diversion was also performed. EVIDENCE SYNTHESIS: Seven trials enrolling 974 patients were included. No differences in terms of major oncological and perioperative outcomes between RARC and ORC were observed. However, length of hospital stay was significantly shorter (MD -0.95; 95%CI -1.32, -0.58) and estimated blood loss lower (MD -296.66; 95%CI -462.59, -130.73) for RARC. Operative time was overall shorter for ORC (MD 89.52; 95%CI 55.88, 123.16), however no difference emerged between ORC and RARC with intracorporeal urinary diversion. CONCLUSIONS: Despite several limitations due to heterogeneity and possible unaddressed confounding in included trials, we concluded that ORC and RARC represent equally valid options for the surgical treatment of patients with advanced bladder cancer.