Background: High-flow nasal oxygen (HFNO) therapy is an upcoming modality used among patients with respiratory failure. The utility of this equipment in intensive care units (ICUs) is undergoing global scrutiny through trials. This article provides descriptive detail about its usage and factors affecting its outcome in an Indian ICU setting. Aims: The aim is to assess the use of HFNO therapy in managing respiratory failure in an ICU setting. Settings and Design: This is a single-center, retrospective, descriptive study in a tertiary care teaching hospital. Patients and Methods: All data of patients who received HFNO therapy between August 2015 and April 2017 were extracted from hospital medical records. Association of HFNO therapy failure rates with age, sequential organ failure assessment (SOFA) score, diagnosis, PaO2/FiO2, PaCO2, and duration of HFNO therapy was analyzed. Data were also analyzed for association of HFNO therapy duration with ICU length of stay and ICU mortality. Results: No significant relation was found between HFNO failure and age, diagnosis, SOFA score, PaO2/FiO2, or PaCO2 levels at initiation of HFNO therapy. Increased HFNO therapy failure rate was found in the first 2 days of HFNO therapy (40.4%) when compared to HFNO therapy use > 2 days (8.7%) (P = 0.006). No significant association was found between duration of HFNO therapy use and length of stay or mortality in the ICU. Conclusions: HFNO is an effective technique to manage respiratory failure in the ICU setting. Severe hypoxia and hypercapnia may effectively be managed using HFNO therapy. Most HFNO therapy failures occur as early as 48 h after initiation of therapy. Prolonged HFNO therapy use does not prolong ICU stay or affect patient mortality.