Abstract Background High-flow nasal oxygen therapy (HFNC) may be an attractive first-line ventilatory support in COVID-19 patients. However, HNFC use for the management of COVID-19 patients and risk factors for HFNC failure remain to be determined. Methods In this retrospective study, we included all consecutive COVID-19 patients admitted to our intensive care unit (ICU) in the first (Mars-May 2020) and second (August 2020- February 202) French pandemic waves. Patients with limitations for intubation were excluded. HFNC failure was defined as the need for intubation after ICU admission. The impact of HFNC use was analyzed in the whole cohort and after constructing a propensity score. Risk factors for HNFC failure were identified through a landmark time-dependent cause-specific Cox model. The ability of the 6-h ROX index to detect HFNC failure was assessed by generating receiver operating characteristic (ROC) curve. Results 200 patients were included: HFNC was used in 114(57%) patients, non-invasive ventilation in 25(12%) patients and 145(72%) patients were intubated with a median delay of 0 (0–2) days after ICU admission. Overall, 78(68%) patients had HFNC failure. Patients with HFNC failure had a higher ICU mortality rate (34 vs. 11%, p = 0.02) than those without. At landmark time of 48 and 72 h, SAPS-2 score, extent of CT-Scan abnormalities > 75% and HFNC duration (cause specific hazard ratio (CSH) = 0.11, 95% CI (0.04–0.28), per + 1 day, p 75%. The risk of HFNC failure could not be predicted by the 6-h ROX index but decreased after a 48-h HFNC duration.