Background: Investigate factors associated with treatment outcome in patients with nontuberculous mycobacterial pulmonary disease (NTMPD). Methods: This retrospective cohort study examined NTMPD patients in Shanghai from January 2014 to December 2018. The distribution and incidence of the different causative species were determined. The outcomes of patients infected with different NTM species were compared. Univariate and multivariate binary logistic regression analyses were used to determine the odds ratios (ORs) and 95% confidence intervals (CIs) for the association of different factors with treatment failure. Results: The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, P<0.001) and M. abscessus (36.1%, P<0.001). Multivariate analysis indicated the risk factors for treatment failure were pathogenic NTM species (M. abscessus: aOR=9.355, P<0.001; MAC: aOR=2.970, P=0.021), having an elevated ESR (>60mm/h: aOR=2.658, P<0.001), receipt of retreatment (aOR=2.074, P<0.001), middle-aged and elderly (>60 years-old: aOR=1.739, P=0.021; 45–60 years-old: aOR=1.661, P=0.034). Conclusions: The main bacterial species responsible for NTMPD infections in Shanghai were MAC, M. abscessus, and M. kansasii. Patients with M. kansasii infections had a higher rate of treatment success. Multiple factors including infection by M. abscessu or MAC, an elevated ESR, receiving retreatment, middle-aged and elderly were associated with treatment failure.