BACKGROUND: Targeted temperature management (TTM) is recommended in the management of out-of-hospital cardiac arrest (OHCA) when coma persists after the return of spontaneous circulation. In the setting of extracorporeal membrane oxygenation (ECMO) for OHCA patients, TTM is associated with good neurological outcomes and is recommended in the Extracorporeal Life Support Organization guidelines. However, the optimal targeted temperature for these patients has not yet been adequately investigated. This study aimed to compare the impact of different targeted temperatures on the outcomes in OHCA patients receiving ECMO. METHODS: This was a retrospective analysis of data from the Japanese Association for Acute Medicine (JAAM)-OHCA Registry, a multicentre nationwide prospective database in Japan in which 103 institutions providing emergency care participated. OHCA patients aged ≥ 18 years who required ECMO with TTM between June 2014 and December 2019 were included in our analysis. The primary outcome was 30-day survival with favourable neurological outcomes, defined as a Glasgow-Pittsburgh cerebral performance category score of 1 or 2. Patients were divided into two groups according to their targeted temperature: normothermic TTM (n-TTM) (35-36 °C) and hypothermic TTM (h-TTM) (32-34 °C). We compared the outcomes between the two targeted temperature groups using multivariable logistic regression and inverse probability weighting (IPW). RESULTS: A total of 890 adult OHCA patients who received ECMO and TTM were eligible for our analysis. Of these patients, 249 (28%) and 641 (72%) were treated with n-TTM and h-TTM, respectively. The proportions of patients with 30-day favourable neurological outcomes were 16.5% (41/249) and 15.9% (102/641), in the n-TTM and h-TTM groups, respectively. No difference in neurological outcomes was observed in the multiple regression analysis [adjusted odds ratio 0.91, 95% confidence interval (CI) 0.58-1.43], and the result was constant in the IPW (odds ratio 1.01, 95% CI 0.67-1.54). CONCLUSION: No difference was observed between n-TTM and h-TTM in OHCA patients receiving TTM with ECMO. The current understanding that changes to the targeted temperature have little impact on the outcome of patients may remain true regardless of ECMO use.