Introduction: The “chain of survival” is a 5-link theoretical construct that has been central to cardiac arrest resuscitation for over 40 years. Although the role of each link has been extensively studied, little is known about the impact of performing the chain of survival in sequence. The purpose of this study was to estimate the proportion of out-of-hospital cardiac arrest (OHCA) responses by Emergency Medical Services (EMS) that had an intact chain of survival sequence response, and the effect of this on survival to hospital discharge. Methods: We conducted a prospective cohort study of adult (>age 20 years) OHCA patients using data collected between 2005-2007 by the Resuscitation Outcomes Consortium (ROC). ROC is a research network involving 10 research sites and 264 EMS agencies across North America. Using routinely collected data, we coded cases as receiving an intact or non-intact chain of survival sequence based on EMS cardio pulmonary resuscitation (CPR), rhythm analysis or defibrillation, epinephrine administration or endotracheal intubation, and transport to a hospital with an electrophysiology lab or percutaneous coronary intervention capability, contingent on the patient’s condition when EMS arrived. Multiple variable logistic regression was performed, adjusting for known (Utstein) survival predictors, to estimate the independent effect of intact chain of survival sequence on survival to hospital discharge. REB approval was obtained. Results: We enrolled12,821 OHCA cases, of which, 29.4% (n=3,773) had an intact chain of survival and 7.6% (n=972) survived to hospital discharge. Cases with an intact chain of survival were younger, and more likely to arrest in public, receive bystander CPR, occur in the USA and specific ROC sites, and had faster EMS response times. The adjusted odds ratio of survival to hospital discharge with an intact chain of survival sequence was 2.4 (95% CI: 2.1-2.8). A sensitivity analysis of 4,056 cases with known timing of endotracheal intubation found a similar adjusted odds ratio of 2.1 (95% CI: 1.6-2.8). Conclusion: Our results indicate that OCHA resuscitation with an intact chain of survival occurs in approximately 1/3 of cases, and results in over a two-fold increase in the odds of surviving to hospital discharge. Initiatives to improve EMS teamwork and increase the proportion of OHCA resuscitation with an intact chain of survival appear to be warranted.