Background: Quality of life (QOL) assessment after radical cystectomy (RC) and urinary diversion (UD) is a crucial element of a fully evaluated patient-reported outcomes and gauging the impact and success of the diversion surgery. There has been long-standing interest in health-related quality of life (HRQOL) evaluation and research among patients who receive UD. Objective: To compare ureterocolic versus orthotopic neobladder (ONB) urinary diversions in terms of their QOL. Patient and method: This retrospective, multicenter study included 128 patients with muscle invasive bladder cancer (MIBC) who underwent RC and UD through the period from January 2011 to June 2016. The patients were divided into two groups: (ONB) 78 patients and uretrosigmoidostomy group 50 patients. HRQOL was evaluated with Functional Assessment of Cancer Therapy–Bladder Cancer (FACT-BL) Questionnaire, while Sexual Health Inventory for Men (SHIM) Questionnaire was used to assess the erectile function of males. Results: The mean patients' age was 54.0 ± 7.9 years old in the ONB group and 57 ± 8.5 years old in ureterosigmoidostomy group. Patients in the ONB group were younger than those in the ureterosigmoidostomy group. There were diff erences in the physical, social and functional well-being that were significantly higher in patients in the ONB. Regarding the sexual function, there were significant differences between patients who underwent nerve sparing RC and non-nerve sparing RC. Conclusions: Findings suggest that patients with an ONB have marginal QOL advantages over ureterosigmoidostomy.