Abstract: BACKGROUND: Feeding tolerance among premature infants is unpredictable using clinical parameters. Ghrelin, a peptide hormone, acts on the hypothalamus to increase hunger and gut motility. It is present in fetal tissues, promotes intestinal maturation, and is secreted in milk. We hypothesized that higher serum ghrelin levels on days 0–7 are associated with improved feeding tolerance and growth in premature infants. METHODS: Infants (< 1500 g birth weight, n = 36) were recruited on day (D) 0–7. Serum ghrelin was measured by ELISA on D 0–7, D 10–14, and D 24–32, and milk ghrelin in a feeding concurrent with each serum sample. Feeding tolerance was assessed as days to first and full enteral feeds. Growth was quantified as both weight and adipose and muscle deposition by ultrasound. RESULTS: Mean serum ghrelin levels decreased from D 0–7 to D 24–32. Higher ghrelin levels on D 0–7 were correlated with shorter time to first enteral feeding, but not with time to full enteral feeds, rate of weight gain, or rate of accretion of muscle or adipose tissue. Milk ghrelin was not related to serum ghrelin or growth. Abdominal and suprascapular muscle and adipose increased during the first month, but weight gain correlated only with the rate of accretion of abdominal adipose. CONCLUSIONS: Elevated serum ghrelin in the first days of life may contribute to gut motility and readiness to feed. Weight gain in premature infants may primarily indicate abdominal fat accumulation, suggesting that ultrasound measurement of muscle accretion is a better marker for lean body growth.