Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and atomoxetine 80 mg/day (Cohort 2) in young adults with ADHD. Results: Adults aged 19 to 25 years with AD/HD (N = 19) who were administered MAS XR significantly improved overall simulated driving performance versus placebo up to 12 hours after dosing. In contrast, there were no statistically significant differences in simulated-driving-performance scores between atomoxetine and placebo. At endpoint, MAS XR reduced ADHD Rating Scale scores [greater than or equal to] 30% in 80% of subjects, whereas atomoxetine achieved this level of improvement for 40%. Limitations: Small sample size and use of simulated driving may limit generalizability of the findings. Conclusion: MAS XR in young adults with ADHD yields significant improvements in simulated driving performance and ADHD symptoms. (Contains 3 tables and 5 figures.)