Background: The aim of the study was to describe and contrast the brain development and outcome among very preterm infants that were and were not exposed to surgery requiring general anesthesia prior to term equivalent age (TEA). Methods: Preterm infants born ≤30 weeks’ gestation who did (n = 25) and did not (n = 59) have surgery requiring general anesthesia during the preterm period were studied. At TEA, infants had MRI scans performed with measures of brain tissue volumes, cortical surface area, Gyrification Index, and white matter microstructure. Neurodevelopmental follow-up with the Bayley Scales of Infant and Toddler Development, Third Edition was undertaken at 2 years of corrected age. Multivariate models, adjusted for clinical and social risk factors, were used to compare the groups. Results: After controlling for clinical and social variables, preterm infants exposed to surgical anesthesia demonstrated decreased relative white matter volumes at TEA and lower cognitive and motor composite scores at 2-year follow-up. Those with longer surgical exposure demonstrated the greatest decrease in white matter volumes and lower cognitive and motor outcomes at age 2 years. Conclusions: Very preterm infants who required surgery during the preterm period had lower white mater volumes at TEA and worse neurodevelopmental outcome at age 2 years. Impact: In very preterm infants, there is an association between surgery requiring general anesthesia during the preterm period and reduced white mater volume on MRI at TEA and lower cognitive and motor composite scores at age 2 years.It is known that the very preterm infant’s brain undergoes rapid growth during the period corresponding to the third trimester.The current study suggests an association between surgery requiring general anesthesia during this period and worse outcomes.