<b><i>Background:</i></b> Magnetic resonance imaging (MRI) is the standard neuroimaging technique to assess perinatal asphyxia-associated brain injury in full-term infants. Diffusion-weighted imaging (DWI) is most informative when assessed during the first week after the insult. <b><i>Objectives:</i></b> To study the DWI abnormalities of the thalamus and basal ganglia in full-term infants with perinatal asphyxia. <b><i>Methods:</i></b> Fifty-five (near) term infants (normothermia <i>n</i> = 23; hypothermia <i>n</i> = 32) with thalamus and/or basal ganglia injury were included. MRI findings were assessed visually and quantitatively calculating apparent diffusion coefficient (ADC) values. Thalamus/basal ganglia ADC ratios were calculated to analyze the differences between these areas. Infants with an early MRI (days 1–3) or later MRI (days 4–7) were compared. <b><i>Results:</i></b> Isolated extensive thalamic injury was seen early, and focal thalamic and basal ganglia injury was seen later. On the early MRI, visual assessment underestimated abnormalities in the basal ganglia (59% abnormal vs. 90% abnormal on quantitative assessment; <i>p</i> = 0.015), suggesting the need for quantitative assessment. In infants treated with hypothermia, the thalamus/basal ganglia ADC ratio was lower. <b><i>Conclusions:</i></b> Both visual analysis and quantitative evaluation of cerebral MRI after perinatal asphyxia are needed, especially during the first few days after birth. Timing of ADC changes is influenced by therapeutic hypothermia.