A geographical epidemiological study was conducted in the 11 departments covered by a comprehensive cancer registry between 1998 and 2011 (more than 4,400 municipalities and 18,000 cancer cases) to analyze the relationship between the incidence of bladder cancer and exposure to chlorination byproducts (CBPs) present in tap water, by sex. Exposure to CSPs was approximated by the average concentration of trihalomethanes (THMs) between 1955 and 1995, estimated based on current concentrations and assumptions regarding changes in chlorination practices. An adjustment was made for smoking and recognized risk factors for this cancer. The shape of the relationship between concentration and cancer risk changes direction with increasing THM concentration. A stratified analysis by water source (surface water or groundwater) reveals two distinct water qualities in terms of health risk, with a positive association for THMs in surface water, bordering on statistical significance. The observed risk is approximately four times lower than the published individual risks. The impact of the most significant biases on the risk estimate is difficult to determine, but the failure to account for residential history could underestimate it. The context of uncertainty regarding the nature of the toxicants involved in bladder cancer risk and their health impact highlights the ongoing need for toxicological and epidemiological research on SPCs. The Constances cohort offers promising prospects for studying this risk in France.