To determine whether time-to-intubation was associated with higher ICU mortality in patients with COVID-19 on mechanical ventilation due to respiratory insufficiency. We conducted an observational, prospective, single-center study of patients with confirmed SARS-CoV-2 infection hospitalized with moderate to severe ARDS, connected to mechanical ventilation in the ICU between March 17 and July 31, 2020. We examined their general and clinical characteristics. Time-to-intubation was the time from hospital admission to endotracheal intubation. We included 183 consecutive patients; 28% were female, and median age was 62 years old. Eighty-eight patients (48%) were intubated before 48 h (early) and ninety-five (52%) after 48 h (late). Patients intubated early had similar admission PaO2/FiO2 ratio (123 vs 99; p = 0.179) but were younger (59 vs 64; p = 0.013) and had higher body mass index (30 vs 28; p = 0.006) compared to patients intubated late. Mortality was higher in patients intubated late (18% versus 43%), with admission PaO2/FiO2 ratio < 100 mmHg (OR 5.2; p = 0.011), of older age (OR 1.1; p = 0.001), and with previous use of ACE inhibitors (OR 4.8; p = 0.026). In COVID-19 patients, late intubation, Pafi <100, older age, and previous ACE inhibitors use were associated with increased ICU mortality. •Time to intubation maybe associated with an increase in mortality in hypoxemic COVID-19 patients.•COVID-19 patients > 60 years-old, admitted with PaO2FiO2 ratio < 100 may have higher ICU mortality when intubated after 48 h.•Patients admitted with PaO2FiO2 ratio < 100 intubated > 48 h have worse lung mechanics than similar patients intubated < 48 h.