Background: There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature. Methods: Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months. Results: Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] 50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1 >50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062). Conclusions: NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.