Preterm children are at risk for social-emotional difficulties, including autism and attention-deficit/hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via magnetic resonance imaging (MRI) at term-equivalent postmenstrual age (TEA), to later social-emotional difficulties.MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birth weight <1,250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. A total of 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy and apparent diffusion coefficient. Social-emotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5 years.Higher apparent diffusion coefficient in the right orbitofrontal cortex was associated with social-emotional problems at age 5 years (peer problems, p < .01). In females, smaller hippocampal volume was associated with increased hyperactivity (p < .01), peer problems (p < .05), and SDQ total score (p < .01). In males, a smaller frontal region was associated with poorer prosocial (p < .05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had social-emotional problems in similar domains at age 2 and those who did not.Early alterations in regional cerebral development in very preterm infants relate to specific deficits in social-emotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.