AimTo use a novel methodology to assess the incidence and specific causes of Out-of-Hospital Cardiac Arrest (OHCA) within a young urban cohort. MethodsAll EMS attended OHCA patients in a large urban area, between 2009 and 2012, aged 2–45 years, treated or untreated, who died or survived, and that were designated as “no obvious cause” etiology by trained data abstractors were included. Using multisource (medical and coroner) records, an expert panel adjudicated the causes of the OHCAs as: confirmed cardiac causes, confirmed non- cardiac causes, and other causes. ResultsOf a total of 1993 cases EMS designated as “no obvious cause”, only 29.9% (595/1993) were due to confirmed cardiac causes; the rest were due to other causes (non-cardiac etiologies): confirmed drug overdose (n=624), trauma (n=108), cancer (n=69), complex chronic care (n=65) and non-cardiac acute illness – mostly vascular, infectious, and metabolic (n=376). The annual incidence rate of “no obvious cause” OHCAs after initial field classification was 12.97/100,000 pt. years (95% CI 12.40, 13.50), compared to 3.87/100,000 pt. years (95% CI 3.56, 4.18) for the confirmed cardiac OHCAs after adjudication. The predominant underlying etiologies of confirmed cardiac OHCAs were coronary heart disease and structural heart disease. ConclusionsIn young adults with OHCA, confirmed cardiac causes were responsible in a minority of cases, and they differed in presentation from those with confirmed non- cardiac causes. Establishing rigorous case ascertainment strategies with linkage to multiple data sources will facilitate a more reliable evaluation of the causes of these events.