Annual influenza epidemics contribute to a substantial global burden of illness and death. This study aims to evaluate clinical outcomes among patients with severe influenza, comparing those who received extracorporeal membrane oxygenation (ECMO) with those who did not. A retrospective study was conducted at Kaohsiung Chang Gung Memorial Hospital involving adult patients diagnosed with influenza between 2015 and 2019. The inclusion criteria encompassed patients with influenza exhibiting severe clinical manifestations. Of 52 severe influenza patients, 51 (98.1%) were invasively ventilated; acute respiratory distress syndrome (ARDS) was identified in 50 (96.2%) patients, and acute kidney injury was identified in 37 (71.2%) patients. Among these patients, 27 (51.9%) died. A subset of 16 (30.8%) patients was treated with ECMO, with 14 (87.5%) infected with the influenza A virus and 12 (75%) receiving oseltamivir ≥48 hours after illness onset. All ECMO patients had pneumonia and required mechanical ventilation, with 14 (87.5%) developing ARDS. The median duration of ECMO support was 9 days. Patients treated with ECMO were significantly younger compared with those not receiving ECMO (P = 0.015). No significant differences were observed in terms of in-hospital mortality between the groups with and without ECMO (68.8% versus 44.4%). Although ECMO is indicated for patients with ARDS who are unresponsive to conventional therapy, early diagnosis and timely initiation of antiviral treatment are essential to prevent progression to ARDS. This study provides comprehensive understanding and management of severe influenza, advocating for standardized treatment protocols and a multidisciplinary approach to enhance patient outcomes.