Although smoking is an established risk factor for Mycobacterial infection, the association between smoking and nontuberculous mycobacterial pulmonary disease (NTM-PD) remains unclear. We evaluated the association between smoking and NTM-PD and tuberculosis (TB) using a population-based South Korean nationwide cohort. Using the Korean National Health Insurance Database, we screened individuals over 20years of age who underwent the national health screening program in 2009. Out of 3,774,308 eligible populations, we identified 2,964 and 26,112 cases of newly developed NTM-PD and TB, respectively. We used multivariate Cox proportional hazards models to estimate the adjusted hazard ratios (aHRs) of risk factors for NTM-PD and TB. The incidence rates for developing NTM-PD and TB were 0.08 and 0.68 per 1,000 person-years, respectively. Current smokers (aHR 0.63, 95% confidence interval [CI] 0.56-0.71) and current heavy smokers (≥ 20 pack-years, aHR 0.74, 95% CI 0.63-0.86) were at lower risk for NTM-PD development than never smokers. On the contrary, current smokers (aHR 1.19, 95% CI 1.15-1.23) and current heavy smokers (aHR 1.27, 95% CI 1.22-1.33) had a higher risk for TB development than never smokers. These trends were augmented if individuals started smoking before age 20years. In subgroup analyses stratified by age, these trends were prominent in the 40-64years age range. Current smoking was associated with a decreased risk of NTM-PD and increased risk of TB. These risks were augmented by early smoking initiation and in the middle age population.