Background Many coronavirus disease 2019 (COVID-19) patients suffering acute hypoxemic respiratory failure (AHRF), fail to respond to conventional oxygen therapy (COT). Subsequently, some centers escalate to continuous positive airway pressure (CPAP), while others resort directly to invasive mechanical ventilation (IMV). We conducted a study to compare the use of CPAP versus COT alone in COVID-19- related AHRF. Patients and methods It is a retrospective cohort study of laboratory-confirmed COVID-19 patients suffering AHRF and deemed eligible for IMV escalation at three university hospitals (United Kingdom) during a 3-month period. The primary endpoint was the need for intubation and the secondary endpoint was 60-day mortality. Results In total, 174 patients were included. In total, 84 patients received CPAP (group 1) and 90 received only COT (group 2). Both groups had comparable demographic criteria and disease severity. There was nonsignificant reduction in the need for IMV when using CPAP compared with COT alone (50 vs. 76.6%, P=0.866). Sixty-day mortality was significantly higher in group 2 (25 vs. 37.8%, P=0.02). COT as standalone therapy for COVID-19 patients (group 2) was associated with a significant increased relative risk of death (relative risk 2.14, 95% confidence interval 1.39-3.29) corresponding to a number needed to treat of 3.74 (95% confidence interval 2.47-7.73). Among patients who progressed to IMV, there was no difference in the risk of mortality between the two groups. Conclusion Introducing CPAP rather than escalating FiO2 or endotracheal intubation in COVID- 19 cases refractory to COT is safe and associated with improved mortality. Clinical trials are needed to guide the optimum timing and selection of patients most likely to benefit. [ABSTRACT FROM AUTHOR]