Objective To investigate the effects of post-discharge fortified human milk feeding on growth, common complications, and neuropsychological development in preterm infants with moderate-to-high nutritional risk. Methods Clinical data were retrospectively collected from 320 preterm infants with moderate-to-high nutritional risk who were discharged from the Department of Neonatology, Provincial Hospital Affiliated to Shandong First Medical University between January 2021 and December 2023 and completed a 6-month follow-up. Infants were classified into four groups by nutritional risk level and feeding method: moderate-risk fortified human milk, moderate-risk formula, high-risk fortified human milk, and high-risk formula. Comparisons were conducted between fortified human milk and formula within the same risk level, and between moderate- and high-risk groups within the same feeding method. Results Within the same feeding method, gestational age at birth and birth weight differed significantly between moderate- and high-risk infants (P<0.001). Within the same nutritional risk level, no significant differences were found between fortified human milk and formula groups in gestational age at birth and birth weight (P>0.05). In the fortified human milk groups, corrected gestational age at discharge differed significantly between moderate- and high-risk infants (P<0.05). No significant differences were noted among the four groups in discharge weight, length, or head circumference (P>0.05). Analysis of covariance, adjusting for discharge weight, length, head circumference, and corrected gestational age at discharge, showed no significant differences among the four groups during the 6-month follow-up in growth velocities of weight, length, or head circumference, nor in hemoglobin, 25-hydroxyvitamin D, or alkaline phosphatase measured at 1, 3, and 5 months (P>0.05). Multivariable logistic regression indicated that fortified human milk feeding did not increase the risk of infection (OR=0.66, 95%CI: 0.40-1.08, P=0.097) or feeding intolerance (OR=0.70, 95%CI: 0.45-1.08, P=0.107). At 6 months' corrected age, mental, motor, and behavioral scores did not differ significantly among groups (P>0.05). Conclusions In preterm infants at moderate-to-high nutritional risk, post-discharge fortified human milk feeding does not increase the risk of infection or feeding intolerance, does not differ significantly from formula feeding in short-term catch-up growth or neuropsychological development, and appears clinically feasible and safe.