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Background The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW+) or absence (TW−) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW+ and TW− groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW+ group than in the TW−group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW− group. At 5 years, 53.1% of patients in the TW+ group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW− group (p<0.05). 34 patients in the TW+ group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW+ bronchioles on CT predicted progression of bronchiectasis. Conclusion Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.