Background-The clinical significance of the presence of non-tuberculous mycobacteria in the sputum of patients with cystic fibrosis is unclear. A retrospective case-control study was performed to assess possible risk factors for nontuberculous mycobacteria and its impact on clinical status in patients with cystic fibrosis. Methods-The records of all patients attending the Leeds cystic fibrosis clinics who were positive for non-tuberculous mycobacteria were examined. Each case was matched with two controls for sex, age, and respiratory function at the time of the first non-tuberculous mycobacteria isolate. Details of respiratory function, nutritional status, antibiotic and corticosteroid therapy, Shwachman-Kulczycki (S-K) score, Northern chest radiographic score, and the frequency of isolation of other bacteria and fungi were collected from two years before to two years after the first non-tuberculous mycobacteria isolate. The patients' genotype and the presence of diabetes mellitus were also recorded. Results-Non-tuberculous mycobacteria were isolated from 14 patients out of a cystic fibrosis population of 372 (prevalence = 3.8%). No significant eVect of nontuberculous mycobacteria was seen on respiratory function, nutritional status, or S-K score. There was a significant association with the number of intravenous antibiotic courses received before the first isolate with cases receiving, on average, twice as many courses as controls (cases 6.64, controls 2.86, 95% CI for diVerence 1.7 to 5.9). No significant diVerence was seen between cases and controls for Northern scores, previous steroid therapy, or the incidence of diabetes mellitus. Conclusions-Non-tuberculous mycobacteria infection in patients with cystic fibrosis is uncommon and its clinical impact appears to be minimal over a two year period. Frequent intravenous antibiotic usage is a possible risk factor for colonisation with non-tuberculous mycobacteria.