Abstract Background Neurodevelopmental deficits(NDs) frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities. We aimed to evaluate white matter(WM) microstructural changes in infants with CHD and analyze the relationship between WM microstructural changes and NDs. Methods A total of 40 infants, 20 with CCHD and 20 with ACHD (matched on age and sex), who underwent preoperative DTI scanning were prospectively enrolled in the study. Multiple linear regression analysis were used to investigate the associations between brain microstructural changes and both clinical variables and neurodevelopmental outcomes, assessed with Gesell Developmental Schedules-Third Edition (GDS-III). Results Infants with CCHD showed lower fractional anisotropy (FA) values in the bilateral cingulum hippocampus (CGH), right anterior thalamic radiation (ATR), and forceps minor (fminor) and exhibited poorer performance in adaptive, motor, language, and personal-social behaviors (all P