Background: Radical cystectomy is the standard treatment for bladder cancer patients. The application of designed nursing protocol in dealing with patients with bladder cancer undergoing radical cystectomy can provide simple and more effective measure to improve clinical outcomes and reduce risk of complications. Aim: The study aimed to evaluate the effect of designed nursing protocol on self-reported outcomes among patients with bladder cancer undergoing radical cystectomy. Design: Quasi-experimental research design was utilized to fulfill the aim of this study. Setting: Urology department at Benha University Hospital.  Subject: convenient sample consisted of (43) patients of both sexes with bladder cancer who attended the urology department to undergo radical cystectomy with urinary diversion for six months. Tools of data collection: Two tools were used by the researcher to collect data for this study Tool I: Structured Interviewing questionnaire involving following three parts: Socio Demographic Characteristics, Patients' Clinical Data and Structured Patients Knowledge Assessment.  Tool II: Self-reported outcomes including 3 parts: Numeric Pain Rating Scale, Fatigue scale and World Health Organization Quality of Life BREF Assessment Questionnaire (WHOQOL-BREF) Results: The study revealed that patients' knowledge level regarding radical cystectomy was significantly improved, also a lower pain & fatigue scores besides, improved QoL after implementing designed nursing protocol, As well as a significant correlation between total knowledge with pain, fatigue and quality of life scores among the studied patients post 3 months period of nursing protocol implementation (p value= <0.001**). Conclusion: Implementation of designed nursing protocol was effective in improving knowledge among radical cystectomy patients, in term of significantly high level after nursing protocol implementation, as well as significantly improved health outcomes with lower pain, fatigue score, and a positive impact on patients' quality of life. Recommendations: Continuous evaluation of patients' knowledge regarding peri operation instructions periodically to determine the effect of designed nursing protocol during follow up periods.