BACKGROUND: The HeartRescue Project is a multistate public health initiative focused on establishing statewide out-of-hospital cardiac arrest (OHCA) systems of care to improve case capture and OHCA care in the community, by emergency medical services (EMS), and at hospital level. METHODS AND RESULTS: From 2011 to 2015 in the 5 original HeartRescue states, all adults with EMS-treated OHCA due to a presumed cardiac cause were included. In an adult population of 32.8 million, a total of 64 988 OHCAs-including 10 046 patients with a bystander-witnessed OHCA with a shockable rhythm-were treated by 330 EMS agencies. From 2011 to 2015, the case-capture rate for all-rhythm OHCA increased from an estimated 39.0% (n=6762) to 89.2% (n=16 103; <0.001 for trend). Overall survival to hospital discharge was 11.4% for all rhythms and 34.0% in the subgroup with bystander-witnessed OHCA with a shockable rhythm. We observed modest temporal increases in bystander cardiopulmonary resuscitation (41.8-43.5%, <0.001 for trend) and bystander automated external defibrillator application (3.2-5.6%, <0.001 for trend) in the all-rhythm group, although there were no temporal changes in survival. There were marked all-rhythm survival differences across the 5 states (8.0-16.1%, <0.001) and across participating EMS agencies (2.7-26.5%, <0.001). CONCLUSIONS: In the initial 5 years, the HeartRescue Project developed a population-based OHCA registry and improved statewide case-capture rates and some processes of care, although there were no early temporal changes in survival. The observed survival variation across states and EMS systems presents a future challenge to elucidate the characteristics of high-performing systems with the goal of improving OHCA care and survival.