Objective: To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non-CF bronchiectasis pediatric patients. Methods: A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non-CF bronchiectasis under the age of 18 years with vitamin D deficiency or insufficiency. The primary outcome was to reach the sufficient Vitamin D level, the secondary outcome was to reevaluate bronchiectasis severity by following up the frequency, severity of pulmonary exacerbations and lung function after vitamin D3 supplementation. Results: Forty patients completed the trial. The percentage of improvement of vitamin D level after vitamin D3 supplementation for six months was significantly higher in CF (88.3%) than non-CF bronchiectasis patients (59.82%) (P = 0.03). Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P = 0.001, 0.005) and frequent exacerbations decreased by 15%, 10% (P = 0.327, 0.490), while the forced expiratory volume in 1 (FEV1) significantly increased by 17% and 15% in non CF bronchiectasis and CF patients respectively (p 0.001). Conclusions: Vitamin D3 therapy was effective in decreasing the frequency and severity of pulmonary exacerbations and preserving lung function. Thereby, improving the disease severity even more in non-CF bronchiectasis than CF patients.