The high frequency of cancer bladder among Egyptian patients is related to Bilharzial infestation. Organ confined muscle invasive bladder cancer should be theoretically cured by cystectomy but unfortunately many patients have progressive disease even after apparent radical ablation. Therefore, identification of independent prognostic factors has potential clinical importance, as it can be used to define an individual's risk for tumor progression and to customize appropriate management strategies. Bcl-XL is one of the most important anti-apoptotic members of Bcl-2 family. As few studies have reported a connection between the Bcl-XL expression and bladder cancer, this work is done to verify the relation between Bcl-XL and Bilharzial related bladder cancer, determine its prognostic value and find any correlation between Bcl-XL expression and the pathological prognostic parameters. Also, to show its value as a radio-sensitivity marker. The present study included 100 cystectomy specimens obtained from patients with muscle invasive Bilharzial related bladder cancer who underwent radical cystectomy in the South Egypt Cancer Institute and the Department of Urology at Assiut University Hospital. Those patients were followed either for 2 years after cystectomy or until local recurrence or distant metastasis had occurred. Bcl-XL expression in the tissue specimens detected by immunohistochemical staining was correlated with; the 2 year recurrence-free survival rate, clinicopathological parameters (tumor type, stage, grade, gross picture & regional lymph node infiltration) and response to adjuvant radiotherapy. There was a statistically highly significant negative strong correlation between Bcl-XL expression and the recurrence-free survival (p0.0001 & r = - 0.731) and the response to adjuvant radiotherapy (p0.0001 & r = -0.741). These correlations were stronger in transitional cell carcinoma than in squamous cell carcinoma. A statistically highly significant positive correlation between Bcl-XL expression and tumor grade & iliac lymph nodes infiltration was detected (p = 0.006 & r = 0.271 and p = 0.003 & r = 0.354 respectively). Rabab M. H. El Ghorori et al,. ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ There was a statistically significant correlation between the histopathological tumor type and the Bcl-XL expression which was more in transitional cell carcinoma (p = 0.027 & r = 0.226). There was no statistically significant correlation between Bcl-XL and either tumor stage, tumor size or shape. In conclusion, Bcl-XL expression is a highly significant negative prognostic factor in patients with bilharzial-related bladder cancer and it is a highly significant indicator of radio-resistance. Bcl-XL is significantly correlated to regional lymph nodes infiltration, tumor grade and type.