The aim of this study was to compare the efficiency, safety, and outcomes of the high-flow nasal oxygen cannula (HFNC) and conventional oxygen therapy (COT) after extubation in children. A randomized controlled trial was conducted in a 13 bed pediatric intensive care unit. One-hundred children who underwent extubation were eligible for the study. Patients were divided into HFNC (n=50) and COT (n=50) groups. Basal variables including heart rate (HR), noninvasive blood pressure, respiratory rate (RR), SpO(2), SpO(2)/FiO(2) (SF) ratio, and end tidal CO2 (EtCO2) were obtained initially and recorded at 15, 30, and 45 minutes and at 1, 6, 12 hours, 24 and 48 hours after extubation. SF ratio and SpO(2) increased during the first hour in the HFNC group (p=0.005 and p=0.03, respectively). HR and RR decreased during follow-up in the HFNC group (p=0.001 and p=0.048, respectively). There was no statistically significant difference for PCO2 after extubation between the two groups. PCO2 (p=0.008) and EtCO2 (p=0.018) values at 24-h were different between two groups. At follow-up, HR decreased only in the HFNC group (p=0.001) and was different at 12 and 48 hours (p=0.047 and p=0.01, respectively). Initial modified radiologic atelectasis scores (m-RAS) were higher for the HFNC group and decreased steadily (p=0.001). Extubation failure rates were 4% and 22% for the HFNC and COT groups, respectively (p=0.007). In conclusion, HFNC is better than COT, especially for the restoration of the respiratory and radiologic parameters. Although more expensive, the use of HFNC may have more advantages to reduce the risk of extubation failure in critically ill children compared with COT.