Characteristics of the Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) caused by distinct subspecies remain uncertain. This study was conducted from 2013 to 2015 in three hospitals in Taiwan. Among the 144 patients with MAC-PD, 57(39.6%), 37(25.7%), 37(25.7%), and 13(9.0%) were infected with M. intracellulare subspecies intracellulare (MIsI), M. avium subspecies hominissuis (MAsH), M. intracellulare subspecies chimaera (MIsC), and others, respectively. Patients with MAsH-PD were younger (P = 0.010) with higher human immunodeficiency virus infection rate (27.0%, 0.0%, 0.0% and 7.7% for MAsH-PD, MIsC-PD, MIsI-PD and others, respectively; P < 0.001). Twenty-two (15.3%) patients reported spontaneous culture-negative conversion, but 15 (10.4%) and 33 (22.9%) patients developed radiographic progression and unfavorable outcomes, especially MAsH-PD. The susceptibility rates to clarithromycin and inhaled amikacin were both 98.6%. MAsH demonstrated the lowest rate of resistance to moxifloxacin (66.7%, 97.3%, 89.1% and 92.3% for MAsH-PD, MIsC-PD, MIsI-PD and others, respectively; P = 0.001) and MIsI isolates had the highest rate of resistance to intravenous amikacin (25%, 13.5%, 38.2% and 15.4% for MAsH-PD, MIsC-PD, MIsI-PD and others, respectively; P = 0.024). Pulmonary disease caused by distinct MAC subspecies had different outcomes and drug susceptibility. The local prevalence of species needs to be monitored.