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Purpose: This analysis aimed to evaluate the clinical relevance of the presurgical systemic inflammation response index (SIRI) in individuals undergoing radical cystectomy (RC)., Methods: In this retrospective study, 228 were categorized into 2 cohorts depending on their SIRI levels using the best cut-off determined by the Youden Index. The association between SIRI and lymph node metastasis (N), advanced pT stage (pT3/pT4), and loco-regional extended state were analyzed at the time of surgery. Multivariate Cox regression analysis was performed to evaluate the impact of SIRI on time to relapse, tumor-specific survival, and survival rates. The additional medical advantage was evaluated through decision curve analysis (DCA)., Results: High and low SIRI group was obtained using the best cut-off value (1.71×10 9 /l). On multivariate logistic regression analysis, elevated SIRI was significantly associated with advanced pT stage (P = 0.003) and loco-regional extended state (P = 0.003). On multivariable Cox regression models based on presurgical clinicopathological factors, an augmented SIRI was linked to poorer relapse-free survival (RFS) (P = 0.035), with the improvement of the concordance index just for RFS. In DCAs, incorporating SIRI yielded results equal to or better than those of the model without SIRI for all outcomes models. It demonstrated improvements in net benefit at probability thresholds up to 50% for the model adjusted with preoperative factors for RFS and for postoperative factors in CSS and OS., Conclusions: SIRI is an innovative prognostic indicator and a potential biomarker that can enhance conventional medical pathological evaluation and improve the personalization of clinical treatment strategies for bladder cancer patients following RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)