The oropharyngeal administration of colostrum (OAC) in neonates has several benefits. To investigate the short-term outcomes of OAC in preterm neonates. We performed this two-arm, double-blind, placebo-controlled randomized trial at a tertiary neonatal center in Iran in 2021-2023. The intervention and control arms received 0.2 mL of their mother's colostrum or distilled water via oropharyngeal administration every 6 h for 3 days starting from birth until 72 h of age. The main study outcomes were neonatal death, the incidence of necrotizing enterocolitis (NEC), sepsis, retinopathy of prematurity (ROP), length of hospital stay, and period to full enteral feeding. A regression analysis was used to adjust for possible confounders. A total of 126 neonates (mean gestational age, 30.05 weeks) were randomized to the intervention and placebo groups (n=63 each) and had a mean ± SD weight of 1247 ± 193 vs 1156 ± 215 g (P=0.013) and 1- and 5-min Apgar scores of 6.35 vs 5.38 (P=0.003) and 7.84 vs 7.13 (P=0.001), respectively. The mortality rate was 12.7% in the intervention group versus 14.3% in the placebo group (P=0.794). The NEC rate was significantly lower in the intervention versus placebo arm (11.1% vs. 28.6%, respectively; P=0.010), as was the clinically suspected sepsis rate (15.9% vs. 39.7%, respectively; P=0.004). The ROP and bronchopulmonary dysplasia rates did not differ significantly between groups after the adjustment for confounders. The mean length of hospital stay was shorter in the intervention group (26.1 vs. 37.32; P=0.023). Moreover, the mean duration of antibiotic therapy and period to full feeding were significantly shorter in the intervention group. OAC could effectively decrease the incidence of complications in preterm infants and facilitate earlier patient discharge.