BACKGROUND: Hypothermia therapy improves mortality and functional outcome after cardiac arrest and birth asphyxia in adults and newborns. The effect of hypothermia therapy in infants and children with cardiac arrest is unknown. METHODS AND RESULTS: A 2-year, retrospective, 5-center study was conducted, and 222 patients with cardiac arrest were identified. Seventy-nine (35.6%) of these patients met eligibility criteria for the study (age >40 weeks postconception and <18 years, cardiac arrest >3 minutes in duration, survival for > or = 12 hours after return of circulation, and no birth asphyxia). Twenty-nine (36.7%) of these 79 patients received hypothermia therapy and were cooled to 33.7+/-1.3 degrees C for 20.8+/-11.9 hours. Hypothermia therapy was associated with higher mortality (P=0.009), greater duration of cardiac arrest (P=0.005), more resuscitative interventions (P<0.001), higher postresuscitation lactate levels (P<0.001), and use of extracorporeal membrane oxygenation (P<0.001). When adjustment was made for duration of cardiac arrest, use of extracorporeal membrane oxygenation, and propensity scores by use of a logistic regression model, no statistically significant differences in mortality were found (P=0.502) between patients treated with hypothermia therapy and those treated with normothermia. Also, no differences in hypothermia-related adverse events were found between groups. CONCLUSIONS: Hypothermia therapy was used in resuscitation scenarios that are associated with greater risk of poor outcome. In an adjusted analysis, the effectiveness of hypothermia therapy was neither supported nor refuted. A randomized controlled trial is needed to rigorously evaluate the benefits and harms of hypothermia therapy after pediatric cardiac arrest.