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Introduction The pre-treatment neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse pathology or survival in a variety of malignancies, including urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Whether the prognostic value of NLR is retained, or even increased, when measured postoperatively remains to be studied. In this study, we evaluated the association of preoperative and postoperative NLR with oncological outcomes following RC. Material and methods The NLR was recorded in 132 consecutive patients with UCB treated with open RC: before surgery (NLR1), postoperatively within 2 days (NRL2), between 7 and 15 days after RC before discharge (NLR3), and a few days before recurrence or last available follow-up (NLR4). Results When assessed by multivariate analysis NLR1 remained independently associated with a significantly increased risk of extravesical disease (pT 3-4) (OR = 1.4, p <0.01) and lymphovascular invasion (LVI) (OR = 1.40, 95% CI 1.09-1.83, p <0.01). NLR4 was independently associated with a significantly increased risk of cancer-specific mortality (CSM) (HR = 1.14, 95%CI 1.03-1.24, p = 0.013). In a postoperative model, NLR3 was found to be an independent predictor of all-cause mortality (ACM) [HR = 1.11, 95% CI 1.02-1.21, p = 0.01]. NLR1 was associated with a significantly increased risk of recurrence in the univariable preoperative model [HR = 1.9, 95%CI 1.00-3.65, p = 0.05], while in the postoperative model NLR4 remained independently associated with a significantly increased risk of recurrence (HR = 1.13, 95%CI 1.04-1.23, p = 0.03). Conclusions In patients with UCB treated with RC, the NLR is associated with more advanced tumour stage, LVI, lymph node metastasis, and higher CSM. Furthermore, the variation of the NLR after surgery might play a role in predicting higher ACM and recurrence-free survival. [ABSTRACT FROM AUTHOR]