BACKGROUND Previous studies have demonstrated the association of abnormalities on diffusion-weighted MRI (DW-MRI) and proton magnetic resonance spectroscopy (1H-MRS) in infants with perinatal asphyxia. The use of therapeutic hypothermia might change this association. OBJECTIVE To study the association between DW-MRI and 1H-MRS and outcome after perinatal asphyxia and therapeutic hypothermia in infants with a gestational age of ≥36 weeks. METHODS Infants with perinatal asphyxia and therapeutic hypothermia (n=88) were included when an MR examination was performed within 7 days after birth. Apparent diffusion coefficient (ADC) values of the basal ganglia and thalamus were calculated, as were lactate/N-acetylaspartate (LAC/NAA) and N-acetylaspartate/choline (NAA/Cho) ratios. Death or an abnormal neurodevelopment at ≥24 months was considered an adverse outcome. Receiver operating characteristic analysis was performed to determine cut-off levels. RESULTS Of the 88 infants, 22 died and 7 had an adverse neurodevelopmental outcome. In infants with an adverse outcome, ADC values of the basal ganglia and thalamus were significantly lower, and Lac/NAA ratios were significantly higher than in infants with a normal outcome. Areas under the curve of ADC of the basal ganglia, thalami and Lac/NAA ratio were 0.89, 0.88 and 0.87, respectively. NAA/Cho ratios were in this cohort not associated with outcome. CONCLUSIONS During and after therapeutic hypothermia, low ADC values and high Lac/NAA ratios of the basal ganglia and thalamus are associated with an adverse outcome in infants with perinatal asphyxia.