The effect of vitamin E supplementation on bilirubin levels in infants was previously explored, but the results were inconclusive. To examine the effect of vitamin E supplementation on bilirubin levels in term infants in the neonatal intensive care unit (NICU). This interventional double-blind randomized clinical trial was conducted in the Sanandaj Besat Hospital NICU. Enrolled newborns were between 37 and 42 weeks and 6 days of gestation and required phototherapy according to American Academy of Pediatrics clinical guidelines. A total of 138 infants were randomly assigned to vitamin E (n=68) or placebo (n=70) groups. In addition to phototherapy, the vitamin E group received 0.5 mL (5 IU) of supplemental vitamin E daily, whereas the placebo group received 0.5 mL of oral dextrose daily. STATA 17 was used for the data analysis. Changes in bilirubin levels at 24 hours postintervention did not differ significantly from baseline in either group. Vitamin E supplementation did not significantly reduce total bilirubin levels at 24 hours postintervention (mean difference [MD], -0.18; P=0.204; 95% confidence interval [CI], -1.39 to 1.02). However, the vitamin E group exhibited lower total bilirubin levels than the placebo group at 48 hours postintervention (MD, 0.18; P=0.365; 95% CI, -0.89 to 1.27) and 72 hours (MD, 0.36; P=0.356; 95% CI, -2.34 to 1.61), although the differences were not statistically significant. A subgroup analysis revealed that female infants experienced a greater reduction in total bilirubin levels than male infants. Infants administered vitamin E versus placebo demonstrated similar reductions in bilirubin levels and hospital stays. Although the average bilirubin changes did not differ significantly between groups, the vitamin E group showed a more noticeable reduction over time, indicating a positive effect of vitamin E supplementation on serum bilirubin reduction. Trial registration: IRCT20220806055625N2 (registered December 26, 2022; http://irct.ir/trial/67135).