Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is one of the frequent complications in patients with muscle-invasive bladder cancer (MIBC) and we previously have reported the negative impact of NAC-induced AKI on oncological outcomes. However, its risk factors remain unclear. Methods: This multi-institutional retrospective study included 517 patients with MIBC who received 2–4 cycles of NAC followed by radical cystectomy. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed any stage AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable logistic regression analysis was performed to identify the risk factors for NAC-induced AKI. The predictive abilities for AKI were evaluated using the area under the receiver operating characteristic curve. Results: The median age was 69 years. Of the 517 patients, 188 (36%) received cisplatin-based regimens and 92 (18%) developed any stage AKI. Approximately 86% AKI were stage 1 AKI. In the univariable analyses, hypertension, impaired renal function, and cisplatin-based regimen were significantly associated with increased risk of AKI. In the multivariable analysis, hypertension, impaired renal function, and cisplatin-based regimen were independently and significantly associated with increased risk of AKI (Table). The optimal cutoff value of estimated glomerular filtration rate for AKI was 65.0 mL/min/1.73m². ROC analysis showed that the AUC of hypertension plus eGFR <65.0 mL/min/1.73m² plus cisplatin-based regimen was 0.748 (95% confidence interval [CI]: 0.697–0.799]. Conclusions: Hypertension, impaired renal function, and cisplatin-based regimens were risk factors for NAC-induced AKI in patients with MIBC.