Extracorporeal membrane oxygenation (ECMO) for trauma is underreported in Latin America. We conducted a cohort study in four centers from Argentina (2015–2024), including all adults with polytrauma (defined as Injury Severity Score [ISS] ≥ 16) who developed acute respiratory distress syndrome (ARDS) with refractory respiratory failure and received veno-venous ECMO. Extracorporeal membrane oxygenation-related complications, in-hospital mortality, and prognostic performance of established scores were assessed retrospectively; long-term health-related quality of life (QoL) was assessed prospectively. Thirty-one patients were analyzed. Bleeding occurred in 25.8% (major in 16.1%); oxygenator/circuit thrombosis in 22.6%. In-hospital mortality was 38.7% (95% confidence interval [CI]: 22–58). Discrimination was modest: area under the ROC curve (AUROC; 95% CI) of 0.62 (0.42–0.82) for ISS, 0.55 (0.33–0.76) for Acute Physiology and Chronic Health Evaluation II (APACHE II), and 0.53 (0.32–0.73) for respiratory ECMO survival prediction (RESP)-score. Among 19 survivors, 11 (57.9%) completed follow-up a median of 7 years after discharge; EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility had a median of 0.743 (bootstrap 95% CI: 0.653–0.831), and Katz Index was 6, indicating preserved independence despite frequent pain/anxiety. Extracorporeal membrane oxygenation achieved 59% in-hospital survival with durable functional status, but the limited prognostic performance of established predictive models highlights the need for trauma-specific tools and structured rehabilitation and follow-up. Limitations include a small sample size and substantial loss of follow-up, restricting precision and generalizability.