Background: According to guidelines and bystander skill, two different methods of cardiopulmonary resuscitation (CPR) are feasible: standard CPR (S-CPR) with mouth-to-mouth ventilations and chest compression-only CPR (CO-CPR) without rescue breathing. CO-CPR appears to be most effective for cardiac causes, but there is a lack of evidence for asphyxial causes of out-of-hospital cardiac arrest (OHCA). Thus, the aim of our study was to compare CO-CPR versus S-CPR in adult OHCA from medical etiologies and assess neurologic outcome in asphyxial and non-asphyxial causes.Methods: Using the French National OHCA Registry (RéAC), we performed a multicenter retrospective study over a five-year period (2013 to 2017). All adult-witnessed OHCA who had benefited from either S-CPR or CO-CPR by bystanders were included. Non-medical causes as well as professional rescuers as witnesses were excluded. The primary end point was 30-day neurological outcome in a weighted population for all medical causes, and then for asphyxial, non-asphyxial and cardiac causes.Results: Of the 8 541 subjects included for all medical causes, 6 742 had a non-asphyxial etiology, including 5 904 of cardiac causes, and 1 799 had an asphyxial OHCA. Among all subjects, 8.6%; 95% CI [8.1-9.3] had a good neurological outcome (i.e. cerebral performance category of 1 or 2). Bystanders who performed S-CPR began more often immediately (89.0%; 95% CI [87.3-90.5] versus 78.2%; 95% CI [77.2-79.2]) and in younger subjects (64.1 years versus 65.7; p < 0.001). In the weighted population, subjects receiving bystander-initiated CO-CPR had an adjusted relative risk (aRR) of 1.04; 95% CI [0.79-1.38] of having a good neurological outcome at 30 days for all medical causes, 1.28; 95% CI [0.92-1.77] for asphyxial etiologies, 1.08; 95% CI [0.80-1.46] for non-asphyxial etiologies and 1.09; 95% CI [0.93-1.28] for cardiac-related OHCA.Conclusions: We observed no significant difference in neurological outcome when lay bystanders of adult OHCA initiated CO-CPR or S-CPR, whether the cause was asphyxial or not.