BACKGROUND: Nontuberculous mycobacteria (NTM) infections in patients with cystic fibrosis (CF) is increasing globally. However, the related epidemiology, comorbidities, and clinical impact of NTM infection remains unclear in the progress of CF lung disease and patient survival. METHODS: We performed a retrospective, case-control, cohort study (10 years), comparing NTM culture-positive CF patients (N = 28) to matched controls (N = 26). NTM positive patients were divided in to two groups of slow-growing (N = 17) and rapid- growing NTM (N = 8). Three patients were positive for both slow and rapid NTM. For independent group comparisons, a non-parametric Mann-Whitney test (Kruskal-Wallis test for more than two groups) was used to compare the continuous variables, and a Fisher's exact test was used for the categorical variables. Paired comparisons were performed using a Wilcoxon signed-rank test. RESULTS: The prevalence of NTM isolation was 8%. The age at CF diagnosis was significantly lower in the slow-growing NTM group compared to the rapidly growing NTM group (P = 0.04). The median percent predicted forced expiratory flow of 25% - 75% (FEF25-75) was significantly higher before NTM acquisition in slow-growing (P = 0.013) and rapidly growing NTM group (P = 0.028). The slow-growing NTM group received significantly more penicillin/beta lactamase (P = 0.010) and rifampin (P = 0.042) following isolation. Macrolide use was significantly higher after isolation in both the slow-growing NTM (P = 0.018) and rapidly growing NTM groups (P = 0.042). CONCLUSIONS: An earlier CF diagnosis was associated with a higher isolation of slow-growing NTM and greater antimicrobial use after infection. NTM acquisition is associated with a worsening of FEF25-75. Thus, both the early diagnosis and treatment of an NTM infection in patients with CF may positively impact lung function.