Background: High flow nasal cannula (HFNC) provides a high flow of humidified and heated oxygen. The use of HFNC allows respiratory failure patients required mechanical ventilation a chance to delay intubation. We compared the hospital outcomes of critical ill patients with HFNC therapy, early failure or late failure. Methods: We performed a retrospective observational study of patients receiving HFNC therapy in a tertiary hospital between January 2013 and March 2014. We selected intubated patients for the failure of HFNC therapy and classified the patients into two groups depending on the timing of intubation, intubation before and after 48 hours. Results: A total of 615 patients receiving HFNC therapy were enrolled in our study. Among them, 175 patients clinically deteriorated despite HFNC therapy and finally received endotracheal intubation. Before 48 hours, 130 patients (74.3%) were intubated and after 48 hours, 45 patients (25.7%) were intubated. There were no significant differences in baseline characteristics between two groups except higher diabetes mellitus (33.85% vs. 15.56%, p=0.02) and Sequential Organ Failure Assessment (SOFA) score day 1 (9.81±3.82 vs. 8.07±3.85, p=0.009) in the patients with intubation before 48 hours. The patients with intubation before 48 hours had higher extubation (37.69% vs. 15.56%, p=0.006) and ventilator weaning rate (55.38% vs. 28.89%, p=0.002), lower ICU mortality (39.23% vs. 66.67%, p=0.001), and longer ventilator free days (8.58±10.06 vs. 3.62±7.48, p=0.011). Conclusions: In a patient with clinically deterioration during HFNC therapy, delayed failure may cause bad outcome and harmful.