Infections by nontuberculous mycobacteria (NTM) are primarily acquired from environmental sources, including exposure to municipally treated drinking water. Higher levels of NTM have been reported in drinking water disinfected with monochloramine than in that disinfected with chlorine. However, the relationships between water treatment practices and NTM infection are unclear. The objective of this study was to examine a possible relationship between residual disinfectant used for municipal drinking water treatment (monochloramine or chlorine) and NTM infection. We retrospectively reviewed NTM diagnostic tests performed at a single health care center during a 15-year period. Information on municipal water treatment practices, including disinfectant and primary source water type, was obtained for 140 cities. Based on a logistic regression model, municipal drinking water disinfection with monochloramine compared to chlorine was not associated with NTM infection (P = 0.24). An additional model variable examining water source showed that the likelihood of having an NTM infection was 1.46 times higher for patients residing in cities with drinking water derived from surface water than for those residing in cities with drinking water derived from groundwater (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.03 to 2.08; P = 0.04). In an inverse propensity score weighted regression, monochloramine disinfection was also not associated with NTM infection. A moderate effect on NTM infection rates was observed in the weighted regression for municipal drinking water derived from surface water, though the results were not statistically significant (OR, 1.24; 95% CI, 0.92 to 1.69; P = 0.17).IMPORTANCE Infections by nontuberculous mycobacteria (NTM) result in significant morbidity, mortality, and health care costs. NTM are primarily acquired from environmental sources, including exposure to municipally treated drinking water. Higher levels of NTM have been reported in drinking water disinfected with monochloramine than in drinking water disinfected with chlorine. Our results suggest that municipal drinking water disinfection with monochloramine compared to chlorine is not associated with higher risk of NTM infection. This is important given that regulations that limit drinking water concentrations of disinfection by-products, which are formed primarily when chlorine disinfection is used, incentivize drinking water utilities to change from chlorine disinfection to monochloramine disinfection. Copyright © 2019 Kotlarz et al.