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The natural history of nontuberculous mycobacteria (NTM) respiratory infection in the general population is poorly understood.To describe the long-term clinical, microbiologic, and radiographic outcomes of patients with respiratory NTM isolates.We previously identified a population-based cohort of patients with respiratory NTM isolation during 2005-2006 and categorized patients as cases or noncases using the American Thoracic Society/Infectious Diseases Society of America pulmonary NTM disease criteria at that time. During 2014-2015, we reviewed medical charts of patients alive on January 1, 2007. Outcomes of interest were the proportion of baseline noncases who later met case criteria and the proportions of patients with culture conversion or findings consistent with persistent disease at least 2-5 years and at least 5 years after first isolation. We defined disease persistence radiographically as infiltrate, nodules, or cavities and microbiologically as a positive respiratory mycobacterial culture. We used logistic regression to evaluate factors associated with evidence of persistence.The study included 172 patients (62% of 278 eligible); those not included either refused consent (n = 47) or were not located (n = 56). One hundred two (59%) included patients met case criteria at baseline. Mycobacterium avium complex was commonly isolated among baseline cases (n = 91 [89%]) and noncases (n = 52 [74%]). Overall, 57 (55%) baseline cases had died, as compared with 43 (61%) noncases (P = 0.47). Among baseline noncases, only four (5.7%) later met case criteria. Overall, 55 (54%) baseline cases and 6 (9%) noncases initiated NTM treatment. Among cases, cultures were converted in 25 (64.1%) treated versus 4 (40%) untreated patients (P = 0.04). Of 89 cases alive 2 years after isolation, 61 (69%) had additional radiography, and 35 (39%) had respiratory cultures. Of these individuals, 54 (89%) had radiographic evidence and 17 (49%) had microbiologic evidence of disease persistence at 5 years after first isolation. These figures were 36 (82%) and 13 (54%), respectively. Women were more likely to have persistent radiographic findings and microbiologic persistence, and patients with chronic obstructive pulmonary disease were less likely to have microbiologic persistence.In the general population, follow-up beyond 2 years of patients with respiratory NTM isolation is limited. Among those with additional evaluations, at least half of individuals have persistent positive cultures or radiographic findings consistent with NTM at least 2 years after isolation.