Background: Previous studies have shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various cancer entities in the metastatic setting, yet there is no evidence on the prognostic value of baseline HRQOL for patients undergoing radical cystectomy (RC) with curative intent. The goal of this study was to evaluate the influence of baseline preoperative HRQOL on cancer specific survival prognosis for patients undergoing RC. Methods: 407 patients with prospectively assessed baseline HRQOL prior RC were included. Patients were stratified by the global health status (GHS) domain of the EORTC QLQ-C30 questionnaire, and good general HRQOL was defined as GHS≥70 based on validated cut-off levels. A 1:2 propensity-score-matched analysis of n=357 patients [n=125 (GHS≥70), n=232 (GHS<70)] was performed. Primary endpoint was cancer-specific survival (CSS), secondary endpoints encompassed overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression models were performed to assess prognostic significance of baseline GHS on survival outcomes. Harrell’s discrimination C-index was assessed to calculate the predictive accuracy of the model (p<0.05). Results: Median follow-up was 40.5mo. Patients subcohorts were well-balanced. All baseline QLQ-C30 functioning scales were in favour of the GHS≥70 cohort (each p<0.001). 5-yr CSS (82% vs. 65%; p=0.001), 5-yr OS (76% vs 53%; p=0.001) and 5-yr-RFS (50% vs. 39%; p=0.04) and were significantly increased in the GHS≥70 cohort. GHS≥70 was confirmed as an independent predictor for increased CSS (HR 0.43, 95%CI 0.21–0.89; p=0.028), OS (HR 0.56, 95%CI 0.31–0.90; p=0.031) and RFS (HR 0.52, 95%CI 0.31–0.87; p=0.013) multivariate analysis. Conclusions: Our findings suggest preoperative baseline HRQOL to have a pronounced predictive value for patients undergoing RC with curative intent for bladder cancer. We found baseline good general HRQOL to accurately predict increased CSS, OS and RFS.