Resuscitation by laypersons is important in bridging the time between the occurrence of an out-of-hospital cardiac arrest (OHCA) and the arrival of emergency rescue service personnel. Depending on the reason for the cardiac arrest, however, the effectiveness of chest compressions is uncertain. The aim of this study was to explore the impact of lay resuscitation on survival following OHCA of different causes. The data set for analysis comprised all cases of cardiac arrest before the arrival of emergency rescue service personnel that were fully documented in the German Resuscitation Registry in the period 2007-2019. The following endpoints related to resuscitation by bystanders were evaluated-separately for each cause-descriptively and by means of multivariate logistic regression analysis: return of spontaneous circulation (ROSC), 30 days' survival/discharged alive from the hospital, and good neurological function at discharge. Altogether, 40 604 cases of cardiac arrest were included. Resuscitation by laypersons was carried out in 35.1% of these cases. The rate of ROSC was statistically significantly higher after lay resuscitation for OHCA caused by cardiac events, drowning, intoxication, or central nervous system disorders (overall 48.1% versus 41.0%). For all causes-with the exception of trauma/bleeding to death and sepsis- the endpoint 30 days' survival/discharged alive was better with lay resuscitation (overall 17.0% versus 9.5%). In multivariate regression analysis, lay resuscitation was associated with improvement of the endpoint 30 days' survival/discharged alive only for OHCA caused by cardiac events (odds ratio [OR] 1.16) or intoxication (OR 1.81). For all other causes-except hypoxia-lay resuscitation tended to yield better results. Neurological function at discharge was also significantly better (overall 11.5% versus 6.1%) after lay resuscitation for OHCA of all causes except trauma/ bleeding to death, hypoxia, and sepsis. Resuscitation by laypersons is associated with an improved result regarding the endpoint 30 days' survival/discharged alive in cases of OHCA caused by cardiac events and intoxication. These two groups account for 81% of the resuscitation patients in the study. Because there was also a tendency towards higher survival rates following OHCA of other causes (except hypoxia), laypersons should continue to be encouraged to attempt resuscitation in all cases of OHCA, whatever the cause.