Objective: To evaluate the efficacy of high frequency oscillatory ventilation (HFOV) in management of acute respiratory distress syndrome and determine whether if there is any superiority over the conventional mechanical ventilation (CMV). Data sources: A systematic review and meta-analysis were conducted according to PRISMA checklist and the Cochrane Handbook for Systematic Reviews of Interventions. The search of the literature was performed through several search databases: PubMed, MEDLINE via Ovid, and web of science. Study selection:We assessed the eligibility of all the relevant studies based on our inclusion and exclusion criteria. The methodological index for nonrandomized studies (MI-NORS) was used to assess the quality of the included studies. The quality and reliability assessment of the included studies were analyzed and appraised Quality Appraisal of Reliability Studies (QAREL) checklist.Data extraction: Meta-analysis was conducted to compare CMV and HFOV in term of in hospital or 30-days mortality, therapy failure, ventilation related complications, and change in PaCO 2 and PaO 2 :FiO 2 ratio. Data synthesis: Twenty studies, involving 2153 patients, were eligible. 59.4% of the included patients received HFOV for management of acute respiratory distress syndrome. The mean age of the included patients was 52.2-years-old. The mortality rate of 45.9% was reported in HFOV group while 46.5% in CMV group. HFOV was associated with increase in risk of therapy failure and hemodynamically instability, with 17% and 53%, respectively. There was a slight decline in quality MINORS total score over the publication years (r = 0.00048, P = 0.94, CI = -0.6908 to 0.6516). Meta-analysis revealed that High frequency oscillatory ventilation would have the same risk of mortality as compared to conventional mechanical ventilation. (RR = 0.93, 95% CI: 0.71 to 1.21, P = 0.60). Conclusion:High Frequency Oscillatory ventilation showed increase risk of therapy failure, when compared to CMV. However, there was not any significant difference between the two groups in term of mortality rate.