OBJECTIVES: To study the long-term impact of psychostimulant treatment on substance abuse and school outcomes in a population-based cohort of AD/HD cases. METHODS: Subjects included 282 AD/HD research identified cases treated with psychostimulant medication and 81 AD/HD cases that were never treated with psychostimulants. These subjects are subsets of the 363 research identified cases from a population-based birth cohort, born in Rochester, MN 1976-1992 who remained in Rochester after age 5 (N = 5,718). All 363 cases were followed from age 5 until emigration, death, school graduation, drop out. Among 282 treated with stimulants, 85% (N = 239) of cases were treated with methylphenidate. Data on type of psychostimulant, dosage prescribed (Methylphenidate Equivalent Units), start/stop dates were collected from medical and school records. The same resources were retrospectively and longitudinally examined for the documentation of substance abuse and school outcomes. Associations between psychostimulant treatment and outcomes were evaluated using general linear and logistic regression models. RESULTS: Of the AD/HD cases treated with stimulants, 16.3% had documented substance abuse compared to 23.5% cases not treated (OR = 0.6; 95% CI = 0.3-1.2; p = 0.14). Cases treated at an earlier age were less likely to have documented substance abuse (p = 0.025) as well as those treated for a longer duration (p = 0.17). Cases with higher average daily psychostimulant dosage had higher reading scores (r = 0.14, p = 0.025). Cases treated with psychostimulants were absent significantly less than those who were not treated (p = 0.024). Furthermore, cases treated longer were absent less (r = -0.18, p = 0.003). CONCLUSIONS: Our large, longitudinal, population-based, study demonstrates that psychostimulant treatment is associated with decreased substance abuse and improved school outcomes among AD/HD cases. Our study confirms the positive impact and importance of long-term treatment with psychostimulants and reflects an improvement in the lives of children with AD/HD.