Insulin-like growth factor (IGF)-I represents one of the most important growth regulators, playing a central role in fetal and neonatal growth. Plasma IGF-I levels increase rapidly after birth, and they are influenced by numerous factors, including sex, age, nutritional state, and premature birth. The aims of this study were: (1) to evaluate the IGF-I plasma profile in healthy newborn foals during the first 2 weeks of life; (2) to assess the possible influence of sex and birth weight on this hormone; (3) to analyze the percentage increment of IGF-I values in healthy foals; (4) to evaluate the influence of prematurity on IGF-I profile; (5) to verify the role of IGF-I as a diagnostic marker of prematurity; and (6) to analyze the percentage increment of IGF-I in premature foals. Thirty-four healthy term foals were enrolled as the control group and from each foal plasma was collected within 6 hours from birth, at 12 hours, daily from Day 1 to Day 7, and at Days 10 and 14 after birth. Eleven foals aged younger than 1 week and diagnosed as premature and hospitalized at a Equine Perinatology Unit were also enrolled; from each foal plasma was collected daily from the day of admission to discharge or death. Insulin-like growth factor I was analyzed by RIA. In the control group, an increasing trend of IGF-I concentrations was found, with higher values from Day 4 to 10 compared with data obtained at less than 6 hours of life, and from Day 5 to 10 compared with 12 and 24 hours and 3 days. No differences were found in healthy foals analyzed in relation to birth weight and sex. In premature foals an increasing trend was observed but no statistical differences were found among sampling times, and no differences were found between healthy and premature foals. The IGF value in premature foals at admission was always higher compared with the lowest recorded level in healthy age-matched foals, thus this parameter does not seem to have a diagnostic role for prematurity in foals. Finally, the evaluation of the percentage increment of IGF-I concentrations showed a significant increase in full-term foals on Day 5, 6, 7, and 10 compared with 12 and 24 hours, and no differences were observed in premature foals. In conclusion, prematurity in newborn foals seems to affect only partially IGF-I plasma concentrations and it does not seem to be a reliable marker for this pathological condition.