CONTEXT Despite 2 decades of evidence demonstrating benefits from prompt coronary reperfusion, registries continue to show that many patients with ST-segment elevation myocardial infarction (STEMI) are treated too slowly or not at all. OBJECTIVE To establish a statewide system for reperfusion, as exists for trauma care, to overcome systematic barriers. DESIGN AND SETTING A quality improvement study that examined the change in speed and rate of coronary reperfusion after system implementation in 5 regions in North Carolina involving 65 hospitals and associated emergency medical systems (10 percutaneous coronary intervention [PCI] hospitals and 55 non-PCI hospitals). PATIENTS A total of 1164 patients with STEMI (579 preintervention and 585 postintervention) eligible for reperfusion were treated at PCI hospitals (median age 61 years, 31% women, 4% Killip class III or IV). A total of 925 patients with STEMI (518 preintervention and 407 postintervention) were treated at non-PCI hospitals (median age 62 years, 32% women, 4% Killip class III or IV). INTERVENTIONS Early diagnosis and the most expedient coronary reperfusion method at each point of care: emergency medical systems, emergency department, catheterization laboratory, and transfer. Within 5 regions, PCI hospitals agreed to provide single-call catheterization laboratory activation by emergency medical personnel, accept patients regardless of bed availability, and improve STEMI care for the entire region regardless of hospital affiliation. MAIN OUTCOME MEASURES Reperfusion times and rates 3 months before (July to September 2005) and 3 months after (January to March 2007) a year-long implementation. RESULTS Median reperfusion times significantly improved according to first door-to-device (presenting to PCI hospital 85 to 74 minutes, P < .001; transferred to PCI hospital 165 to 128 minutes, P < .001), door-to-needle in non-PCI hospitals (35 to 29 minutes, P = .002), and door-in to door-out for patients transferred from non-PCI hospitals (120 to 71 minutes, P < .001). Nonreperfusion rates were unchanged (15%) in non-PCI hospitals and decreased from 23% to 11% in the PCI hospitals. For patients presenting to or transferred to PCI hospitals, clinical outcomes including death, cardiac arrest, and cardiogenic shock did not significantly change following the intervention. CONCLUSIONS A statewide program focused on regional systems for reperfusion for STEMI can significantly improve quality of care. Further research is needed to ensure that programs that result in improved application of reperfusion treatments will lead to reductions in mortality and morbidity from STEMI.