This study — perhaps the most well-known of all HighScope research efforts — examines the lives of 123 children born in poverty and at high risk of failing in school.

From 1962–1967, at ages 3 and 4, the subjects were randomly divided into a program group that entered a high-quality preschool program based on HighScope's participatory learning approach, and a comparison group who received no preschool program. Published in Lifetime Effects, the study's most recent phase — the HighScope Perry Preschool Study Through Age 40 [2005]) — interviewed 97% of the study participants still living at the age of 40. Additional data was gathered from the subjects' school, social services, and arrest records.

The study found that adults at age 40 who underwent the preschool program had higher earnings, committed fewer crimes; were more likely to hold a job, and were more likely to have graduated from high school than adults who did not have a preschool education.