It has been established that adolescents with ADHD are at high risk for driving accidents. MPH is the most frequently prescribed psychostimulant for the treatment of ADHD. One dose of MPH has been found to improve simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours after ingesting the drug. Little is known, however, about the effects of various MPH delivery profiles on driving performance over the course of a day. This was the objective of the current study. A total of six male drivers with diagnosed ADHD participated in the study. Using a random numbers table, each subject was assigned to receive either MPH in equal doses at 8 a.m., noon, and 4 p.m. (t.i.d.) followed by OROS MPH q.d. at 8 a.m., or OROS MPH q.d. followed by MPH t.i.d. OROS MPH is a once-daily, osmotic, controlled-release oral formulation of MPH that delivers the drug to provide an ascending profile for efficacy lasting through 12 hours. The primary outcome measure was each subject's computer-quantified impaired Driving Score (IDS). Under each treatment condition, participants were maintained on their medication dosage for 7 days, after which they operated a sophisticated driving simulator at 2 p.m., 5 p.m., 8 p.m., and 11 p.m. The study found that IDS worsened in the evenings for participants who received MPH t.i.d., but remained stable when they received once-daily OROS MPH. Participants performed significantly better when receiving OROS MPH q.d. compared with MPH t.i.d., particularly in the evenings. 2 tables, 1 figure, and 35 references