Background: There is growing interest in finding inexpensive, easily reproducible biomarkers to predict outcomes in patients with urothelial bladder carcinoma (BC). An elevated preoperative neutrophil-to-lymphocyte Ratio (NLR) has been found to be an independent prognostic factor for decreased survival, predictive of upstaging at radical cystectomy (RC), and predictive of recurrence and progression. This study investigated the utility of the preoperative NLR predicting long-term outcomes in chemotherapy naïve patients undergoing RC for BC at a large tertiary care center. Methods: In a retrospective cohort study, 849 RC patients with BC were identified between 2000 and 2011. NLR data for these patients was obtained within 30 days prior to RC. Univariate CART analysis was used to determine an NLR cutoff point that was significantly associated with both overall survival (OS) and disease specific survival (DSS). OS and DSS were estimated using Kaplan-Meier curves. Results: The median follow-up time among survivors was 7.3 years. 597 (70%) patients died and 252 (30%) were alive at last follow. Using CART analysis, a preoperative NLR cutoff point of 3.19 was identified to have the strongest association with both OS and DSS (p < 0.001). 562 (66%) patients had a preoperative NLR < 3.19 and 475 (34%) had a preoperative NLR ≥ 3.19. The median OS and DSS for patients with preoperative NLR < 3.19 was 5.96 years and 15.64 years, respectively. The median OS and DSS for patients with a NLR ≥ 3.19 was 4.44 years (95% CI: 3.18-4.81 years) and 8.23 years (95% CI: 5.15-11.87 years). DSS Kaplan-Meier curve was significant, p < 0.001. Patients with a NLR < 3.19 had a 5-year OS and DSS of 59% and 77%, respectively. RC patients with a NLR ≥ 3.19 had a 5-year OS and DSS of 43% and 56%. Conclusions: A preoperative NLR ≥ 3.19 is significantly associated with decreased OS and DSS in patients treated with RC for UC. This finding further validates NLR as a biomarker in BC prognosis. NLR can help to determine patients with a poor prognosis who may benefit from more aggressive, adjuvant therapy following RC.