Nontuberculous mycobacterial (NTM) infections are increasing in disease frequency worldwide. This systematic review examines health-related quality of life (HRQOL), comorbidities and mortality associated with pulmonary NTM disease. We searched MEDLINE, EMBASE, CINAHL, Scopus Life Sciences, conference proceedings and Google (earliest date available to February 2015) for primary studies. Eligible studies compared populations with and without pulmonary NTM disease in high-income jurisdictions. We excluded studies on HIV/AIDS. All languages were accepted. Two reviewers followed MOOSE and PRISMA reporting guidelines and independently appraised quality using STROBE. All studies were summarized qualitatively regardless of quality. Of 3193 citations screened, we included 17 studies mostly from Taiwan (n= 5) and the USA (n= 4). Two studies assessed HRQOL; one assessed comorbidities, 11 assessed mortality, and three assessed multiple outcomes. Populations with pulmonary NTM reported significantly worse or similar HRQOL than the general population, depending on the instruments used. Some suggested greater prevalence of having bronchiectasis (n= 2) and greater risk of developing pulmonary tuberculosis (n= 1). Most (n= 7) suggested no difference in mortality, although only one was age-matched and gender-matched to the general population. Four suggested NTM populations had higher mortality—two of which compared with the general population and were deemed of high quality, while two compared with non-NTM patients from hospital. High clinical heterogeneity in study design may explain discordant results. Bias assessments and controlling for confounding were carried out poorly. No consistent trends were observed although there is suggestion of an increased health burden from respiratory diseases and increased mortality associated with pulmonary NTM disease.