BackgroundEffective bystander cardiopulmonary resuscitation (CPR) improves outcomes in out-of-hospital cardiac arrest (OHCA) patients. However, the effect of CPR training on the rate of return of spontaneous circulation (ROSC) among laypersons has yet to be thoroughly evaluated. MethodsThis prospective, multicenter observational study was conducted across 42 centers in Japan. We assessed OHCA patients who received bystander CPR from a layperson, excluding those performed by healthcare staff. The primary outcome was the ROSC rate. Secondary outcomes included pre-hospital ROSC, ROSC after hospital arrival, favorable neurological outcomes, and 30-day survival. Propensity score with inverse probability treatment weighting (IPTW) was used to adjust for confounders, including age, sex, presence or absence of witnesses, and past medical history. ResultsA total of 969 OHCA patients were included, divided into CPR-trained (n = 322) and control (n = 647). Before adjustment, the ROSC rate was higher in the trained group than the control (40.1% vs. 30.1%, P < 0.01). After IPTW adjustment, the trained group showed a significantly higher ROSC rate (36.7% vs. 30.6%; P = 0.02). All secondary outcomes in the trained group were significantly improved before adjustment. After IPTW adjustment, the trained group showed improved rates of pre-hospital ROSC and ROSC after hospital arrival (30.7% vs. 24.0%; P < 0.01, 23.9% vs. 20.7%; P = 0.04). There were no differences in neurological outcomes and 30-day survival. ConclusionThis study demonstrated that CPR training for laypersons was associated with increased ROSC rates in OHCA patients, indicating potential advantages of CPR training for non-healthcare professionals.