ABSTRACT: This study aimed to investigate the prognostic difference between AUTOPULSE and LUCAS for out-of-hospital cardiac arrest (OHCA) adult patients.A retrospective observational study was performed nationwide. Adult OHCA patients after receiving in-hospital mechanical chest compression from 2012 to 2016 were included. The primary outcomes were sustained return of spontaneous circulation (ROSC) of more than 20?minutes and survival to discharge.Among 142,906 OHCA patients, 820 patients were finally included. In multivariate analysis, female (OR, 0.57; 95% CI, 0.33-0.99), witnessed arrest (OR, 2.10; 95% CI, 1.20-3.69), and arrest cause of non-cardiac origin (OR, 0.25; 95% CI, 0.10-0.62) were significantly associated with the increase in ROSC. LUCAS showed a lower survival than AUTOPULSE (OR, 0.23; 95% CI, 0.06-0.84), although it showed no significant association with ROSC. Percutaneous coronary intervention (OR, 6.30; 95% CI, 1.53-25.95) and target temperature management (TTM; OR, 7.30; 95% CI, 2.27-23.49) were the independent factors for survival. We categorized mechanical CPR recipients by witness to compare prognostic effectiveness of AUTOPULSE and LUCAS. In the witnessed subgroup, female (OR, 0.46; 95% CI, 0.24-0.89) was a prognostic factor for ROSC and shockable rhythm (OR, 5.04; 95% CI, 1.00-25.30), percutaneous coronary intervention (OR, 12.42; 95% CI, 2.04-75.53), and TTM (OR, 9.03; 95% CI, 1.86-43.78) for survival. In the unwitnessed subgroup, no prognostic factors were found for ROSC, and TTM (OR, 99.00; 95% CI, 8.9-1100.62) was found to be an independent factor for survival. LUCAS showed no significant increase in ROSC or survival in comparison with AUTOPULSE in both subgroups.The in-hospital use of LUCAS may have a deleterious effect for survival compared with AUTOPULSE.