Microbiological criteria for nontuberculous mycobacterial pulmonary disease (NTM-PD) require cultures from two separate sputum or one non-sputum specimen. However, there is limited data on the progression of NTM-PD following non-sputum culture-based diagnosis. We compared the disease progression of NTM-PD diagnosed with non-sputum vs sputum cultures. We included 833 patients and divided them into sputum NTM isolation (n = 123), sputum NTM-PD (n = 558), and non-sputum NTM-PD groups (n = 152). Disease progression, defined as radiographic aggravation and therapy initiation, was compared between groups. The median observation time was 60.5 months (interquartile range, 31.4-96.0). The non-sputum NTM-PD group showed longer treatment-free survival (log-rank test; p = 0.009) and lower risk of treatment (adjusted hazard ratio [aHR] of sputum NTM-PD group, 1.36; 95% confidence interval (CI), 1.01-1.84) than the sputum NTM-PD group. The non-sputum NTM-PD group showed longer radiographic aggravation-free survival (Log-rank test; p = 0.015) and lower risk of radiographic aggravation (aHR of sputum NTM-PD group, 1.52; 95% CI, 1.06-2.19) than the sputum NTM-PD group. NTM-PD diagnosed using methods other than sputum culture showed a low risk of disease progression and progressed slower than NTM-PD diagnosed from a sputum culture. NTM-PD diagnosed using methods other than sputum culture may be a mild disease, not equivalent to NTM-PD diagnosed from sputum culture.