Although patients with attention-deficit hyperactivity disorder (ADHD) have reported improved driving performance on methylphenidate, limited evidence exists to support an effect of treatment on driving performance and some regions prohibit driving on methylphenidate. A randomized, crossover trial examining the effects of methylphenidate versus placebo on highway driving in 18 adults with ADHD was carried out. After three days of no treatment, patients received either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo and then the opposite treatment after a six to seven days washout period. Patients performed a 100 km driving test during normal traffic, 1.5 h after treatment administration. Standard deviation of lateral position (SDLP), the weaving of the car, was the primary outcome measure. Secondary outcome measurements included the standard deviation of speed and patient reports of driving performance. Driving performance was significantly better in the methylphenidate than in the placebo condition, as reflected by the SDLP difference (2.3 cm, 95% CI = 0.8-3.8, P = 0.004). Variation in speed was similar on treatment and on placebo (-0.05 km/h, 95% CI = -0.4 to 0.2, P = 0.70). Among adults with ADHD, with a history of a positive clinical response to methylphenidate, methylphenidate significantly improves driving performance.