AIM: To determine which of the approved immune checkpoint inhibitors is the optimal treatment in metastatic urothelial bladder cancer. METHODS & MATERIALS: Only the pivotal Phase III trials of second-line metastatic urothelial bladder cancer were included in this network meta-analysis. RESULTS: This NMA included three pooled trials (NCT00315237, NCT02256436 and NCT02302807) of 1125 participants. Pembrolizumab was the only treatment with positive effect on overall survival compared with the best supportive care. The treatment discontinuation rates due to adverse events of the pembrolizumab and atezolizumab did not differ from that of the best supportive care. C onclusion: Our results confirmed the superiority of pembrolizumab in the management of metastatic urothelial bladder cancer.