BACKGROUND: Nontuberculous mycobacteria (NTM) are opportunistically pathogenic bacteria that are found abundantly in the soil and water. Susceptible individuals exposed to NTM-containing aerosols from environmental sources may develop NTM pulmonary disease (NTM-PD). Reported survival after NTM-PD diagnosis varies widely among existing studies. Prior work has suggested that mortality among persons with NTM-PD is primarily driven by comorbidities rather than NTM-PD. METHODS: We retrospectively identified a cohort of patients in the Duke University Health System who were diagnosed with NTM-PD between 1996 and 2015. Hospitalizations and survival were compared among patients with NTM-PD with and without other comorbidities. Additionally, survival among patients with NTM-PD was compared with standardized mortality data for a similar cohort of the general population. RESULTS: Patients with NTM-PD without other comorbidities had 0.65 hospitalizations/1000 patient-days compared with 1.37 hospitalizations/1000 patient-days for patients with other comorbidities. Compared with a cohort of the general population, expected survival decreased by approximately 4 years for a diagnosis of NTM-PD without comorbidities and 8.6 years for a diagnosis of NTM-PD with comorbidities. Mortality 5 years after diagnosis was 25.0% and 44.9% among NTM patients without and with comorbidities, respectively, compared with 5.7% in the general-population cohort. CONCLUSIONS: NTM-PD was associated with significant morbidity that was worse in patients with comorbidities. Patients with NTM-PD, even without comorbidities, had worse survival than expected.