Aim: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest (CA). Moderate hypothermia (MH) has shown promise in mitigating ischemia-reperfusion injury following CA. The HYPO-ECMO trial aimed to compare the effect of MH versus normothermia in refractory CS rescued by VA-ECMO. The primary aim of this non-predefined post hoc study was to assess the treatment effect of MH in the subgroup of patients with cardiac arrest (CA) within the HYPO-ECMO trial. Additionally, we will evaluate the prognostic significance of CA in these patients. Methods: This post hoc analysis utilized data from the randomized HYPO-ECMO trial conducted across 20 French cardiac shock care centers between October 2016 and July 2019. Participants included intubated patients receiving VA-ECMO for CS for less than 6 hours, with 334 patients completing the trial. Patients were randomized to early MH (33-34°C) or normothermia (36-37°C) for 24 hours. Results: Of the 334 patients, 159 (48%) experienced preceding CA. Mortality in the CA group was 50.9% at 30 days and 59.1% at 180 days, compared to 42.3% and 51.4% in the no-CA group, respectively (adjusted risk difference [RD] at 30 days, 8.1% [-0.8 to 17.1%], p=0.074 and RD at 180 days 7.0% [-3.0 to 16.9%], p=0.17). MH was associated with a significant reduction in primary (RD -13.3% [-16.3 to -0.3%], p=0.031) and secondary outcomes in the CA group only (p<0.025 for all), with a significant interaction between MH and CA status for 180-day mortality [p=0.03]. Conclusions: This post hoc analysis suggests that MH shows potential for reducing mortality and composite endpoints in patients with cardiac arrest and refractory CS treated with VA-ECMO without an increased risk of severe bleeding or infection. Further research is needed to validate these findings and elucidate underlying mechanisms.