Background Venovenous extracorporeal membrane oxygenation (VV-ECMO) should be considered when conventional mechanical ventilation failed to maintain adequate gas exchange. ECMO improved gas exchange and thus preventing hypoxia and ventilator-induced lung injury. Aim To compare between VV-ECMO and conventional mechanical ventilatory support with protective lung strategy in patients with acute respiratory distress syndrome regarding selection of patients, efficacy, complications, and outcome. Patients and methods We retrospectively studied 83 patients referred for VV-ECMO consideration to ECMO center in the ICU in Chest Disease Hospital in Kuwait between January 2015 and October 2018. We had two groups: ECMO group (N=38) and conventional mechanical ventilation group (control group) (N=45). We excluded from ECMO all patients with contraindication to ECMO. After 7 days, five patients shifted to rescue ECMO owing to worsening of their condition. Clinical, laboratory, ventilator parameters, complications, and survival rate were compared between both groups. Result The clinical, laboratory, and ventilator parameters of the patients on randomization were very bad for both groups. After 5 days, significant improvement was recorded among ECMO group. At the end point of the study, weaning from ECMO was successful in 32 (74.4%) of the 43 patients, whereas in the control group, 28 (70%) patients were weaned successfully. Mortality was nonsignificantly higher in the control group (30 vs. 25.6% for ECMO group). The most common fatal complication among ECMO group was bleeding (63.6%), whereas it was respiratory failure among the control group (75%). Advanced age, long duration of mechanical ventilation before ECMO, immunocompromised state, higher blood lactate level and higher Acute Physiology and Chronic Health Evaluation II score, and the underlying lung disease before ECMO were associated with poor outcome. Conclusion VV-ECMO can be considered as an alternative therapy for patients with severe but potentially reversible acute respiratory distress syndrome when conventional ventilation failed. ECMO reduced the risk of ventilator-induced lung injury. ECMO significantly improved most of the clinical, laboratory, and ventilator parameters within days after ECMO application. ECMO had more favorable outcome and lower rate of mortality but with higher complications.