BackgroundDifferences in 30-day survival between males and females following out-of-hospital cardiac arrest (OHCA) are well documented. Biological sex does not appear to be responsible for this survival gap independently of potential mediating factors. We investigated the role of potential mediating factors in the association between sex and 30-day survival after OHCA in Scotland.MethodsA retrospective cohort study of adult non-emergency medical services (EMS)-witnessed OHCA cases was conducted. We included incidents from the whole of Scotland where resuscitation was attempted by the Scottish Ambulance Service (SAS) between April 1, 2011 and March 1, 2020. Logistic regression was used to assess the contribution of age, socioeconomic status, urban–rural location of the incident, initial cardiac rhythm, bystander cardiopulmonary resuscitation (CPR) and location of the arrest (home or away from home).ResultsThe cohort consisted of 20,585 OHCA cases (13,130 males and 7,455 females). Median (IQR) age was 69 years (22) for males versus 72 years (23) for females. A higher proportion of males presented with initial shockable rhythm (29.4% versus 12.4%) and received bystander CPR (56.7% versus 53.2%) compared with females. A higher proportion of females experienced OHCA at home (78.8% versus 66.8%). Thirty-day survival after OHCA was higher for males compared with females (8.2% versus 6.2%). Males had higher age-adjusted odds for 30-day survival after OHCA than females (OR, 1.26; (95% CI), 1.12–1.41). Mediation analyses suggested a role for initial cardiac rhythm and location of the arrest (home or away from home).ConclusionMales had higher age-adjusted 30-day survival after OHCA than females. However, after adjusting for confounding/mediating variables, sex was not associated with 30-day survival after OHCA. Our findings suggest that initial cardiac rhythm and location of the arrest are potential mediators of higher 30-day OHCA survival in males than females. Improving proportions of females who present with initial shockable rhythm may reduce sex differences in survival after OHCA.