To compare postoperative complications and health-related quality of life of patients undergoing robot-assisted radical cystectomy with those of patients undergoing open radical cystectomy. A systematic search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A pooled meta-analysis was carried out to assess the differences between robot-assisted radical cystectomy and open radical cystectomy according to randomized and non-randomized comparative studies, respectively. We identified six randomized comparative studies and 31 non-randomized comparative studies. Most robot-assisted radical cystectomy patients were treated with extracorporeal urinary diversion. Robot-assisted radical cystectomy was associated with longer operative times, and lower blood loss and transfusion rates compared with open radical cystectomy in both randomized comparative studies and non-randomized comparative studies. There was no significant difference between robot-assisted radical cystectomy and open radical cystectomy in the rate of patients with any or major complications within 90 days both in randomized comparative studies and non-randomized comparative studies. Non-randomized comparative studies reported a lower rate of complications at 30 days, mortality at 90 days and length of stay for patients treated with robot-assisted radical cystectomy, which were not confirmed in randomized comparative studies. Additionally, there were no differences in postoperative quality of life score assessment at 3 and 6 months between robot-assisted radical cystectomy and open radical cystectomy. Robot-assisted radical cystectomy is associated with less blood loss and lower transfusion rates. There is no difference in complications, length of stay, mortality, and quality of life between robot-assisted radical cystectomy and open radical cystectomy. Data from non-randomized comparative studies favor perioperative outcomes in robot-assisted radical cystectomy patients, the failure to confirm in randomized comparative studies, likely due to bias in study design and reporting. Further randomized comparative studies comparing postoperative complications and quality of life between robot-assisted radical cystectomy with intracorporeal urinary diversion and open radical cystectomy are required to assess potential differences between these two surgical approaches.