The aim of this study was to distinguish and compare the chest imaging features of non-tuberculous mycobacteria lung disease (NTM-LD) and pulmonary tuberculosis (PTB) in patients with sputum acid fast bacillus (AFB)-smear positive since an earlier differential diagnosis between these two is very important in clinical practice. PATIENTS AND METHODS: A total of 4167 previously untreated cases with AFB smear-positive sputum were collected from January 2011 to January 2014, in Shanghai Pulmonary Hospital, Tongji University, China. Among them, 124 cases were identified with NTM-LD after specimen culture and strain identification. A cohort of 210 patients with PTB was randomly selected from the remaining 4043 cases with PTB as comparator. The clinical and chest computed tomography (CT) imaging data were compared. RESULTS: The most prevalent pathogens in patients with NTM-LD were Mycobacterium abscessus (42%, 52/124) and Mycobacterium intracellulare (34%, 42/124). Univariate analysis showed patients with NTM-LD more frequently had bronchiectasis (85.5% vs. 45.7%, p < 0.001), thin-walled cavity (D ≥ ≥ 3 cm) (16.9% vs. 7.6%, p = 0.011) compared to PTB patients. Additionally, the location of lesion also differed and the right middle lobe (23.9% vs. 16.3%, p < 0.001) and left lingual segment bronchiectasis (19.9% vs. 8.2%, p < 0.001) were more prominent in NTM-LD. Multivariate analysis showed, bronchiectasis (OR = 8.521, 95% CI: 4.209-17.250, p < 0.001) and thinwalled cavity (D ≥ ≥ 3 cm) (OR = 3.561, 95% CI: 1.394-9.097, p = 0.008) were also the independent predictors for the diagnosis of NTM-LD. CONCLUSIONS: Bronchiectasis in the right middle lobe or left lingual segment and thinwalled cavity with a diameter of more than 3 cm are the frequently the chest CT features in patients with NTM-LD, which might be helpful for an early diagnosis in patients with AFB-smear positive.