Background : Egypt is among the countries with the highest incidence of bladder cancer (BC). Adipokines involved in BC development. This study aimed to examine the diagnostic and prognostic roles of irisin in BC through its function as an adipokine. Patients and methods : This study included 150 subjects; 75 patients newly diagnosed as BC and 75 apparently healthy subjects. Serum irisin levels were quantified by enzyme- linked immunosorbent assay. Results : Serum irisin levels exhibited significantly lower levels in BC patients compared to controls (1.07 [0.51-1.96] and 1.8 [0.5-2.44] μg/mL), respectively ( P < 0.001). Serum irisin was positively correlated with BMI (r = 0.386, P = 0.001) and negatively correlated with serum cholesterol (r = −0.58, P < 0.0 0 01). Irisin had 74.7% sensitivity and 90.7% specificity at a cutoffpoint of ≤1.2 μg/mL. Serum irisin levels reduction can predict the BC stages, when adjusted for BMI and serum cholesterol level, serum irisin had an adjusted odds ratio of 14 ( P = 0.001). Low serum irisin patients had a higher mortality rate when compared to those with high levels (38.2% vs 5%). Conclusion : BC patients had significantly lower levels of serum irisin. Serum irisin showed acceptable performance criteria in BC diagnosis. It had a limited role in BC grading but showed a decreasing trend in different BC stages. Serum irisin seems to be an excellent diagnostic and prognostic marker for BC.