Abstract We examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H:quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. We used logistic regression to analyze data from a multi-center case-control study and estimate adjusted odds ratio (OR) and 95% CI (confidence interval) Exposure to pesticides was associated with increased bladder cancer risk (1.68 (1.23-2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79(1.25-2.56) than for squamous cell carcinoma (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85) activities as compared to those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism.