Background: Although neonatal platelets have been shown to be hyporesponsive to most agonists in vitro, several groups have reported shorter closure times (CT) in term cord blood samples than in children and adults. It is unknown whether this is also true for preterm neonates, or for neonates of any gestational age (GA) during the 1st week of life, since limited studies have evaluated neonatal blood samples. Objectives: We designed this study to determine the effects of GA and postconceptional age on platelet function using the platelet function analyzer PFA-100®. Methods: We measured CTs in cord blood samples and in neonatal blood samples of varying GAs on days of life 1–2, and ≧7. Results: CTs were determined in 51 cord blood samples, 34 neonatal blood samples obtained on day of life 1–2, 16 neonatal blood samples from preterm neonates ≧7 days old, and 10 adults. We found a significant inverse relationship between ADP CTs and GA in both cord blood and neonatal blood day of life 1–2 samples (p = 0.02 and p = 0.01, respectively). When cord blood samples were compared with neonatal and adult blood, epinephrine and ADP CTs were significantly longer in adult blood as well as in neonatal samples obtained at either of the two time points (p ≤ 0.01 for all). Conclusions: Platelet function in response to ADP appears to improve with advancing GA. The differences between cord blood and neonatal blood CTs indicate that substantial changes in primary hemostasis occur shortly after birth. The reasons underlying these changes are unknown.