CONTEXT: Bladder-sparing strategies (BSSs) have been proposed for the treatment of muscle-invasive bladder cancer (MIBC) patients achieving clinical complete response (cCR) to initial systemic treatment to avoid toxicity related to radical cystectomy. OBJECTIVE: To systematically review the current literature evaluating oncological outcomes of BSSs in patients achieving cCR to initial systemic treatment for localized MIBC. EVIDENCE ACQUISITION: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting oncological outcomes of MIBC patients undergoing either surveillance or radiation therapy after achieving cCR to initial systemic treatment. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 23 noncomparative prospective or retrospective studies published between 1990 and 2021. The mean bladder and metastatic recurrence rates (range) as well as the mean bladder preservation rate (BPR; range) were calculated, and overall survival (OS) was extracted from included reports. EVIDENCE SYNTHESIS: Overall, 16 and seven studies evaluated surveillance (n = 610) and radiation therapy (n = 175) in MIBC patients achieving cCR to initial systemic treatment, respectively. With regard to surveillance, the median follow-up ranged from 10 to 120 mo, with a mean bladder recurrence rate of 43% (0-71%), including 65% of non-muscle-invasive bladder cancer (NMIBC) and 35% of MIBC recurrences. The mean BPR was 73% (49-100%). The mean metastatic recurrence rate was 9% (0-27%), while 5-yr OS rates ranged from 64% to 89%. With regard to radiation therapy, the median follow-up ranged from 12 to 60 mo, with a mean bladder recurrence rate of 15% (0-29%), including 24% of NMIBC, 43% of MIBC, and 33% of unspecified recurrences. The mean BPR was 74% (71-100%). The mean metastatic recurrence rate was 17% (0-22%), while the 4-yr OS rate was 79%. CONCLUSIONS: Our systematic review showed that only low-level evidence supports the effectiveness of BSSs in selected patients achieving cCR to initial systemic treatment for localized MIBC. These preliminary findings highlight the need for further prospective comparative research to demonstrate its efficacy. PATIENT SUMMARY: We reviewed studies evaluating bladder-sparing strategies in patients achieving complete clinical response to initial systemic treatment for localized muscle-invasive bladder cancer. Based on low-level evidence, we observed that selected patients could benefit from surveillance or radiation therapy in this setting, but prospective comparative research is requested to confirm their efficacy.