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Introduction: Lay rescuers have a crucial role in successful cardiopulmonary resuscitation (CPR), specifically the first three links in the chain of survival, for out-of-hospital cardiac arrest (OHCA). However, randomized controlled trials on the priority of emergency call (Call first) versus bystander CPR (CPR first) do not exist, and comparative data are very limited. We aimed to assess the association between the priority of bystander’s action (Call first vs. CPR first) and neurologic outcome after OHCA.Methods: This nationwide population-based study of patients who experienced OHCA from January 2005 to December 2014 was based on the data from the Japanese government-managed registry of OHCA. Patients provided bystander’s action (both emergency call and bystander CPR) within 1 minute of witness were included, and Call first strategy was compared with CPR first strategy. The primary outcome was one-month neurologically favorable survival, defined as a Glasgow-Pittsburgh cerebral performance category (CPC) score of 1(good performance) or 2(moderate disability). The secondary outcomes were prehospital return of spontaneous circulation (ROSC) and one-month overall survival.Results: A total of 25,840 patients were included; 4,430 (17.1%) were treated with Call first approach, and 21,410 (82.9%) were treated with CPR first approach. Among total cohort, 2,696 (10.4%) survived with neurologically favorable status one month after OHCA. In the propensity score-matched cohort, one-month neurologically favorable survival was lower among Call first group compared with CPR first group: 364 of 4,430 patients (8.2%) vs. 457 of 4,430 patients (10.3%), respectively (Risk ratio [RR], 0.80; 95% confidence interval [CI], 0.70-0.91). Similar associations were observed for one-month overall survival (RR, 0.90; 95%CI, 0.82-0.99), although there were no significant differences in prehospital ROSC (RR, 0.94; 95%CI, 0.86-1.02) between the Call first and CPR first groups. In subgroup analyses, the association between delayed bystander CPR and worse neurological outcome did not change regardless of subgroup characteristics.Conclusions: In witnessed OHCA, Call first approach was associated with a decreased chance of one-month neurologically favorable survival compared with CPR first approach. These observational findings warrant a randomized clinical trial to determine the priority of emergency call or bystander CPR for OHCA.