Background: Pre-operative neutrophil-to-lymphocyte ratio (NLR) has been found to be associated with adverse pathological results and poor long-term outcomes in patients treated with radical cystectomy (RC) for urothelial bladder carcinoma (BC). Prior studies have determined inclusion based on neoadjuvant chemotherapy (NAC) status. This study aimed to evaluate pre-operative NLR in a large cohort without exclusion as a predictor of long-term outcomes in patients undergoing RC for BC. Methods: A retrospective cohort study was performed of 1243 patients undergoing RC between 2000 and 2011. NLR was summarized using descriptive statistics. Univariate classification and regression trees analysis (CART) was applied to identify subgroups of patients using pre-surgery NLR as the covariate and overall survival (OS) or disease specific survival (DSS) as the outcome of interest. The probabilities of OS and DSS were estimated using the Kaplan-Meier method. Results: The median follow-up time among survivors was 7 years. 863 (69%) patients died and 380 (31%) were alive at last follow-up. The median OS was 5.2 years (95% CI: 4.9-5.5 years). Using CART analysis, the strongest association with OS was the cutoff point 3.09. 767 (62%) patients had pre-surgery NLR < 3.09 and 475 (38%) had pre-surgery NLR ≥ 3.09. The overall survival was found to be significantly associated with NLR < 3.09 vs. ≥ 3.09 (p < 0.001). The median OS for patients with NLR < 3.09 and ≥ 3.09 was 5.9 years (95% CI: 5.3-6.3 years) and 4.2 years (95%:3.3-4.7 years), respectively. Patients with NLR < 3.09 and ≥ 3.09 had 5-year OS of 56% and 44%, respectively. DSS was found to be significantly associated with NLR ≥ 3.09 vs. < 3.09 (p < 0.001). The median DSS for patients with pre-surgery NLR < 3.09 and ≥ 3.09 were 15.6 years and 7.5 years, respectively. Conclusions: The NLR significantly predicts OS and DSS in RC patients. NLR should be taken into consideration as NAC and adjuvant treatments are considered in BC patients to help improve survival.