PURPOSE: To determine the effectiveness and harms of bladder-preserving trimodal therapy (TMT) as a first-line treatment versus radical cystectomy (RC) plus radical pelvic lymphadenectomy in the treatment of muscle-invasive bladder cancer in terms of overall survival. METHODS: We included parallel clinical trials and prospective and retrospective cohort studies that included patients older than 18 years old, diagnosed with muscle-invasive bladder cancer, who underwent TMT compared with RC. The planned comparison was TMT versus RC plus pelvic lymphadenectomy as first-line treatment. The primary outcome was overall survival (OS) and secondary outcomes were salvage cystectomy and cancer-specific survival and progression-free survival. A search strategy was designed for MEDLINE, CENTRAL, Embase, and LILACS. We saturated information with conference abstracts, in progress clinical trials, literature published in non-indexed journals, and other sources of gray literature. Standardized tools assessed the risk of bias independently. We performed the statistical analysis in R v3.4.1 and effect sizes were reported in terms of hazard ratios (HR) and the corresponding 95% confidence intervals (95%CI). Accordingly, we used a random effect model due to the statistical heterogeneity found in included studies. RESULTS: We found 2682 records with the search strategies and, finally, 11 studies were included in the quantitative analysis. The summary HR for OS was 1.06 95%CI (0.85-1.31) I2 = 77%, showing no statistical difference. Regarding cancer-specific survival, the summary HR was 1.23 95%CI (1.04-1.46) I2 = 14%. On the other side, for the progression-free survival, the summary HR was 1.11 95%CI (0.63-1.95) I2 = 78%. Only one study described HR for adverse events (1.37 95%CI 1.16-1.59). CONCLUSION: We found no differences in overall survival and progression-free survival between these two interventions. Nonetheless, we found that cancer-specific survival favored patients who received radical cystectomy.