In this multicenter, randomized trial, neonates with moderate or severe hypoxic–ischemic encephalopathy randomly assigned to whole-body hypothermia had a significantly reduced risk of death or moderate or severe disability at 18 to 22 months of age. This study suggests that whole-body hypothermia may improve substantially the outcomes for infants with hypoxic–ischemic encephalopathy. Neonates with moderate or severe hypoxic–ischemic encephalopathy randomly assigned to whole-body hypothermia had a significantly reduced risk of death or moderate or severe disability at 18 to 22 months of age. Among term infants, hypoxic–ischemic encephalopathy due to acute perinatal asphyxia remains an important cause of neurodevelopmental deficits in childhood. Infants with moderate encephalopathy have a 10 percent risk of death, and those who survive have a 30 percent risk of disabilities. Sixty percent of infants with severe encephalopathy die, and many, if not all, survivors are handicapped. 1 , 2 Treatment is currently limited to supportive intensive care. Reductions in brain temperature by 2°C to 5°C provide neuroprotection in newborn and adult animal models of brain ischemia. 3 – 10 Brain cooling has a favorable effect on multiple pathways contributing to brain injury, including . . .