In this single-center retrospective cohort study, we compared extracorporeal membrane oxygenation (ECMO) cannulation and early management performed in the emergency resuscitation room (ERR) versus the intensive care unit (ICU). A total of 105 patients undergoing venoarterial ECMO were analyzed using inverse probability of treatment weighting to reduce baseline imbalance. Patients in the ERR group presented with greater physiological instability, including higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, severe metabolic acidosis, and a predominance of extracorporeal cardiopulmonary resuscitation cases. Although ERR cannulation was associated with significantly higher unadjusted 3 day mortality, this association was attenuated after adjustment for confounders. Baseline physiological variables, particularly arterial pH and the need for precannulation mechanical ventilation, independently predicted mortality, whereas procedural timing and cannulation setting were not significant determinants of outcome. Importantly, rates of bleeding, thrombosis, and infection were comparable between the ERR and ICU groups, suggesting that ECMO cannulation in the ERR can be performed safely by a dedicated experienced team using standardized protocols. These findings indicate that early mortality after ECMO is primarily driven by the severity of precannulation physiological collapse rather than the procedural environment itself, supporting the feasibility and safety of ERR-initiated ECMO in critically unstable patients.