Background and Objective: Milk intolerance due to gastrointestinal dysmotility is a common problem among preterm neonates. Erythromycin has a prokinetic effect on gastrointestinal motility. The purpose of this study was to assess the effectiveness of oral erythromycin in preterm neonates on milk tolerance. Materials and Methods: This clinical trial was conducted on 70 preterm neonates with a gestational age of 28 to 34 weeks who were admitted to the neonatal intensive care unit of Imam Reza (AS) Hospital in Kermanshah, Iran. Thirty-five infants in the control group received breast milk alone and 35 neonates in the treatment group received 2.5mg/kg oral erythromycin every 6 hours for 10 days in addition to breast milk. The time taken to reach full enteral feeding, duration of hospitalization, daily vomiting episodes and residual volume of gastric lavage were compared in the two groups by t- test and chi- square test. Results: There was no significant difference between the two groups regarding their sex distribution, birth weight, gestational age and onset of feeding. Also, there was no significant difference between the two groups in the time to reach full enteral feeding (P=0.058). The number of gastric residue episodes was significantly higher in the control group than in the treatment group (5.11± 2.92 versus 2.23 ± 1.88 P = 0.003). None of the neonates in the two groups developed necrotizing enterocolitis, cardiac arrhythmias, and hypertrophic pyloric stenosis. Conclusion: Prophylactic use of recommended dose of oral erythromycin in preterm neonates with a gestational age of less than 34 weeks reduces gastric residue but does not reduce the time to reach full enteral feeding.