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Background: Take Heart™ America (THA) is a community-based initiative that sequentially deployed all of the most highly recommended 2005 AHA Guidelines in an effort to increase survival from out-of-hospital cardiac arrest (OHCA). We hypothesized that the THA program could be successfully initiated and that OHCA survival rates would be increased after implementation.Methods: The THA program was initiated at two sites in Minnesota with a combined population of 439,692 (greater St. Cloud and Anoka County). Implementation included widespread CPR and automated external defibrillator (AED) skills training in schools and businesses; retraining of EMS personnel in methods to enhance circulation [minimizing CPR interruptions, performing CPR prior to and after single shock defibrillation, use of an impedance threshold device (ITD)]; additional deployment of AEDs in schools and public places; protocols for transport to and treatment by Cardiac Arrest Centers (CACs) for therapeutic hypothermia, coronary artery evaluation and treatment, and electrophysiological evaluation. Survival in patients with OHCA from Nov 2005–June 2009 was evaluated and compared with the year prior to implementation.Results: More than 28,000 people were trained in CPR and AED use. Bystander CPR rates increased from 20% to 29% [p=0.067, Odds ratio (OR) 1.7, 95% Confidence Interval (CI) 0.95, 3.08]. Of 247 total OHCAs, 64% had CPR with use of an ITD. Three CACs were established and 45% of patients were treated with hypothermia. Survival to discharge for patients with OHCA of cardiac etiology improved from 8.4% (9/107, historical control) to 19% (47/247, post-implementation) (p= 0.011, OR 2.56, CI 1.17, 6.17). For those with an initial rhythm of ventricular fibrillation, discharge rates increased from 17% (5/29) to 40% (36/89) (p=0.025, OR 3.26 (1.07, 11.86). Comparing the intervention group with historical controls, 42/94 (45%) vs 8/38 (21%) underwent cardiac catheterization and revascularization. Implantable defibrillators were placed in 22/94 (23%) vs 5/38 (13%).Conclusions: TheTHA program more than doubled OHCA survival when compared with historical controls. Feasibility of generalizing this approach to larger cities, regions, and states is underway.