Abstract： Background Severe acute respiratory syndrome is frequently complicated by respiratory failure requiring ventilatory support. We aimed to compare the efficacy of non-invasive ventilation against invasive mechanical ventilation treating respiratory failure in this disease. Methods Retrospective analysis was conducted on all respiratory failure patients identified from the Hong Kong Hospital Authority Severe Acute Respiratory Syndrome Database. Intubation rate, mortality and secondary outcome of a hospital utilizing non-invasive ventilation under standard infection control conditions (NIV Hospital) were compared against 13 hospitals using solely invasive ventilation (IMV Hospitals). Multiple logistic regression analyses with adjustments for confounding variables were performed to test for association between outcomes and hospital groups. Results Both hospital groups had comparable demographics and clinical profiles, but NIV Hospital (42 patients) had higher lactate dehydrogenase ratio and worse radiographic score on admission and ribavirin-corticosteroid commencement. Compared to IMV Hospitals (451 patients), NIV Hospital had lower adjusted odds ratios for intubation (0.36, 95% CI 0.164-0.791, P=0.011) and death (0.235, 95% CI 0.077-0.716, P=0.011), and improved earlier after pulsed steroid rescue. There were no instances of transmission of severe acute respiratory syndrome among health care workers due to the use of non-invasive ventilation.Conclusion Compared to invasive mechanical ventilation, non-invasive ventilation as initial ventilatory support for acute respiratory failure in the presence of severe acute respiratory syndrome appeared to be associated with reduced intubation need and mortality.