Background We investigated associations between tobacco exposure, history of schistosomiasis and bladder cancer risk in Egypt. Methods We analyzed data from a case-control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression we estimated the covariate-adjusted odds ratios (OR) and 95% confidence interval (CI) of the associations. Results Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (UC) (OR = 1.8, 95% CI = 1.4, 2.2), but not squamous cell carcinoma (SCC); smoking both waterpipes and cigarettes was associated with an even greater risk for UC (OR = 2.9, 95% CI = 2.1, 3.9) and a statistically significant risk for SCC (OR = 1.8, 95% CI = 1.2, 2.6). Among non-smoking men and women, to environmental tobacco smoke exposure was associated with an increased risk of UC. History of schistosomiasis was associated with increased risk of both UC (OR = 1.9, 95% CI = 1.2, 2.9) and SCC (OR = 1.9, 95% CI = 1.2, 3.0) in women and to a lesser extent (OR = 1.4, 95% CI = 1.2, 1.7 and OR = 1.4, 95% CI = 1.1, 1.7, for UC and SCC respectively) in men. Conclusions The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and UC. Impact This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis, and suggests that smoking both cigarettes and waterpipes increases the risk for SCC and UC in Egyptian men.