The current study examines the extent to which participation in preschool at age 4 is associated with blood pressure, body mass index, and awakening cortisol at age 15. We capitalize on data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development to examine differences in adolescent health among children who attended preschool, parental care, or home-based care at age 4 (n = 742). Using quasi-experimental methods, we found that preschool participation was associated with multiple positive health outcomes in adolescence. In particular, preschool participation was associated with lower systolic and diastolic blood pressure and lower arterial pressure during adolescence compared with children in parental care (but not home-based care). Preschool participation was also related to lower levels of cortisol (measured at waking) compared with youth who did not attend preschool. More hours in preschool was associated with higher body mass index and more teacher education is associated with lower teacher education. Results are discussed in terms of how early preschool experiences may help to explain long-term health trajectories.