This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.