Background— Therapeutic hypothermia can improve survival and neurological outcomes in cardiac arrest survivors, but its cost-effectiveness is uncertain. We sought to evaluate the cost-effectiveness of treating comatose cardiac arrest survivors with therapeutic hypothermia. Methods and Results— A decision model was developed to capture costs and outcomes for patients with witnessed out-of-hospital ventricular fibrillation arrest who received conventional care or therapeutic hypothermia. The Hypothermia After Cardiac Arrest (HACA) trial inclusion criteria were assumed. Model inputs were determined from published data, cooling device companies, and consultation with resuscitation experts. Sensitivity analyses and Monte Carlo simulations were performed to identify influential variables and uncertainty in cost-effectiveness estimates. The main outcome measures were quality-adjusted survival after cardiac arrest, cost of hypothermia implementation, cost of posthospital discharge care, and incremental cost-effectiveness ratios. In our model, postarrest patients receiving therapeutic hypothermia gained an average of 0.66 quality-adjusted life years compared with conventional care, at an incremental cost of $31 254. This yielded an incremental cost-effectiveness ratio of $47 168 per quality-adjusted life year. Sensitivity analyses demonstrated that poor neurological outcome postcooling and costs associated with posthypothermia care (in-hospital and long term) were the most influential variables in the model. Even at extreme estimates for costs, the cost-effectiveness of hypothermia remained less than $100 000 per quality-adjusted life year. In 91% of 10 000 Monte Carlo simulations, the incremental cost-effectiveness ratio was less than $100 000 per quality-adjusted life year. Conclusions— In cardiac arrest survivors who meet HACA criteria, therapeutic hypothermia with a cooling blanket improves clinical outcomes with cost-effectiveness that is comparable to many economically acceptable health care interventions in the United States.