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INTRODUCTION The cumulative burden of chronic health conditions could contribute to out-of-hospital cardiac arrest (OHCA) physiology and response to attempted resuscitation. Yet little is known about how chronic health conditions influence prognosis. We evaluated the relationship between cumulative comorbidity and outcome following ventricular fibrillation OHCA using 3 different scales. METHODS We performed a cohort investigation of persons >=18years who suffered non-traumatic OHCA and presented with ventricular fibrillation between January 1, 2007 and December 31, 2013 in a metropolitan emergency medical service (EMS) system. Chronic conditions were ascertained from EMS reports. The primary relationship between cumulative comorbidity and outcome (survival to hospital discharge) used the Charlson Index and two other scales. Analyses used logistical regression (LR), multiple imputation and inverse probability weighting. RESULTS During the study period 1166/1488 potential patients were included. The median Charlson Index was 1 (25th-75th%: 0-2). Overall survival was 43.9%. Comorbidity was associated with a dose-dependent decrease in the likelihood of survival. ompared to Charlson Score of 0, the odds ratio of survival was 0.68 (0.48-0.96) for Charslon of 1, 0.49 (0.35-0.69) for Charlson of 2, and 0.43 (0.30-0.61) for Charlson of >=3 after adjustment for Utstein predictors using multivariable LR. This inverse comorbidity-survival association was similar for the other 2 scales and was observed for different clinical outcomes (admission to hospital, functional survival, 30-day survival, and 1-year survival). CONCLUSION Based on these results, cumulative comorbidity can help explain survival variability and improve prognostic accuracy. Whether information about cumulative comorbidity or specific health conditions can inform resuscitation care is unknown though the results suggest comorbidity may influence acute pathophysiology and treatment response.