OBJECTIVE: To evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) compared to NAC combined with immune checkpoint inhibitors (ICI) in patients with muscle-invasive bladder cancer (MIBC). Propensity score matching (PSM) was employed to assess the impact of these two treatment regimens on the pathological complete response rate (pCR) and overall survival (OS). METHODS: A retrospective analysis was conducted on 320 MIBC patients treated at the Cancer Hospital affiliated to Sun Yat-sen University Gansu Hospital between January 2017 and June 2022. Patients were categorized into the NAC group (n=194) and the NAC+ICI group (n=126) based on their treatment regimens. After PSM, 154 patients were included, with 77 in each group. Baseline characteristics, clinical efficacy, and prognosis were analyzed using various statistical methods. RESULTS: Before PSM, significant differences were observed between the groups in baseline characteristics, including tumor diameter, tumor number, and adjuvant treatment (all P<
0.05). After PSM, these differences were no longer statistically significant (all P>
0.05). The NAC+ICI group demonstrated a significantly higher pCR rate both before and after PSM (both P<
0.001). Similarly, pathological downstaging rates were higher in the NAC+ICI group before and after PSM (both P<
0.001). However, there was no significant difference in disease control rates between the two groups before (P=0.057) and after PSM (P=0.240). Logistic regression analysis identified the treatment regimen (before PSM: P<
0.001, OR=0.161
after PSM: P<
0.001, OR=0.141) and complications (before PSM: P=0.005, OR=2.339
after PSM: P=0.019, OR=2.753) as independent risk factors for pCR. Cox regression analysis revealed that age (before PSM: P<
0.001, HR=1.059
after PSM: P=0.011, HR=1.066), pretreatment T stage (before PSM: P<
0.001, HR=2.342
after PSM: P<
0.001, HR=3.244), tumor diameter (before PSM: P=0.005, HR=1.810
after PSM: P=0.025, HR=2.077), and treatment outcome (before PSM: P<
0.001, HR=1.722
after PSM: P=0.020, HR=1.444) were independent prognostic factors for OS. CONCLUSION: NAC combined with ICI significantly improves pCR and pathological downstaging rates in MIBC patients. Independent prognostic factors affecting OS include age, pretreatment T stage, tumor diameter, and treatment outcome.