Disinfection byproducts (DBPs) and -nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited. We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort. Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen ( ) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS at enrollment ( ; ), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level ( ; TTHM; HAA5; ). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors e.g., body mass index, hormone replacement therapy (HRT), and mutually adjusted for . We evaluated associations for low-grade ( ) vs. high-grade ( ) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation. Higher average concentrations of DBPs (95th percentile: TTHM , HAA5 ) were associated with endometrial cancer risk (TTHM: , 95% CI: 1.41, 3.40; HAA5: , 95% CI: 1.19, 2.83; ). Associations were similarly observed for women greater than median years of PWS use with levels , in comparison with zero years (TTHM: , 95% CI: 1.18, 2.21; HAA5: , 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: , 95% CI: 1.17, 3.83; ) than for high-grade tumors (TTHM: , 95% CI: 0.80, 2.44; ), but differences were not statistically significant ( ). Associations with TTHM were stronger among ever HRT users than non-HRT users ( ). We observed no associations with in drinking water or diet. We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.