BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type Ⅱ lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.