Drug overdose causes approximately 183,000 deaths worldwide annually and 50,000 deaths in Canada and the United States combined. Drug-related deaths are concentrated among young people, leading to a substantial burden of disease and loss of potential life years. Understanding the epidemiology, patterns of care, and prognosis of drug-related prehospital emergencies may lead to improved outcomes. We conducted a retrospective cohort study of out-of-hospital cardiac arrests with drug-related and presumed cardiac causes between 2007 and 2013 using the Toronto Regional RescuNet Epistry database. The primary outcome was survival to hospital discharge. We computed standardized case fatality rates, and odds ratios of survival to hospital discharge for cardiac arrests with drug-related versus presumed cardiac causes, adjusting for confounders using logistic regression. The analysis involved 21,497 cardiac arrests, including 378 (1.8%) drug-related and 21,119 (98.2%) presumed cardiac. Compared with the presumed cardiac group, drug-related arrest patients were younger and less likely to receive bystander resuscitation, have initial shockable cardiac rhythms, or be transported to hospital. There were no significant differences in emergency medical service response times, return of spontaneous circulation, or survival to discharge. Standardized case fatality rates confirmed that these effects were not due to age or sex differences. Adjusting for known predictors of survival, drug-related cardiac arrest was associated with increased odds of survival to hospital discharge (OR1.44, 95%CI 1.15-1.81). In out-of-hospital cardiac arrest, patients with drug-related causes are less likely than those with presumed cardiac causes to receive bystander resuscitation or have an initial shockable rhythm, but are more likely to survive after accounting for predictors of survival. The demographics and outcomes among drug-related cardiac arrest patients offers unique opportunities for prehospital intervention.