Objective: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at high risk for driving accidents. One dose of methylphenidate (MPH) improves simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours post-dose. However, little is known about the effects of different MPH delivery profiles on driving performance throughout the day. Method: This randomized, crossover, single-blind study compared osmotic, controlled-release oral system (OROS) MPH (Concerta) given q.d. to immediate-release MPH (Ritalin) given in equal doses t.i.d. on driving performance among six male ADHD-diagnosed adolescent drivers aged 16 to 19 years. Under each treatment condition, participants were maintained on their medication dosage for 7 days, then drove a sophisticated driving simulator at 2 P.M., 5 P.M., 8 P.M., and 11 P.M. The primary outcome measure was each participant's computer-quantified Impaired Driving Score (IDS). Results: IDS worsened in the evenings for participants receiving 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. (F = 9.3, df = 1, p = .004). When MPH was given t.i.d., IDS significantly worsened beginning at 8 P.M. compared to OROS MPH (p = .01). Conclusions: Participants demonstrated significantly less variability and better driving performance when receiving OROS MPH q.d. compared to MPH t.i.d., particularly in the evenings.