Introduction: Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Prediction of successful weaning in these patients may improve resource use and patients outcome. The Respiratory ECMO Survival Prediction (RESP) score has been proposed as an outcome prediction tool for patients undergoing venovenous (VV-ECMO). However, it was developed and validated on patients established on ECMO. This may limit its usefulness as an adjunct tool for decision-making process at the pre-ECMO stage. Aim: The aim of the work was to assess the efficacy of RESP score as a tool to predict successful weaning in patients treated with VV-ECMO before initiation of treatment.Patients and methods: The study was carried out on 23 adult patients who were admitted to the units of Critical Care Medicine Departments in Egyptian Armed Forces Hospitals within 1 year and were treated with VV-ECMO; all of them received the same treatment as recommended by ELSO guidelines for adult respiratory failure. They were classified into two groups according to ECMO weaning successfulness at the end of the study: group I (successful weaning) and group II (failed weaning). Complete physical assessment, laboratory investigations, and RESP score calculation were done before ECMO initiation. Results: Pre-ECMO RESP score, in group I it ranged from −8 to 7 (mean 1.75 ± 3.65), while in group II it ranged from −11 to 1 (mean −6.38 ± 1.88), there was statistically significant difference between the two groups (p = 0. 003). The ROC curve of RESP score showed an AUC of 0.880 (95% CI 0.658-0.981) (p < 0.001). The best cutoff value was −1, at that level the sensitivity was 69.7%, specificity was 81.5%. Calculated positive predictive value of RESP score was 88.9% while negative predictive value was 63.6%. Conclusion: RESP score may be effective tool to predict ECMO weaning successfulness before initiation of ECMO.