Objective: To evaluate clinical measures of the benefit/risk ratio in a post hoc analysis of a clinical trial of d-threo-methylphenidate hydrochloride (d-MPH) and d,l-threo-methylphenidate hydrochloride (d,l-MPH). Method: Data from a phase III clinical trial was used to compare equimolar doses of d-MPH and d,l-MPH treatment for attention-deficit/hyperactivity disorder (ADHD) on clinician ratings of improvement/deterioration, teacher ratings of remission, and duration of action. Results: d-MPH was clinically and statistically significantly superior to d,l-MPH on clinician's dimensional ratings of global improvement, teacher ratings of remission of ADHD symptoms and parent 6:00 P.M. ADHD symptom ratings. No treatment differences were observed for symptom ratings at 3:00 P.M. and for 6:00 P.M. math test performance. Conclusion: The results suggest that the two drugs may have distinct profiles on the measures analyzed. Because d-MPH may have be more than twice the potency of d,l-MPH, the differences reported here are only applicable to the doses of the study drugs involved in the clinical trial. The results are limited by the exploratory nature of our analysis, small samples, and multiple analyses. The findings are suggestive that further study is warranted to look at these differences prospectively but cannot be used to draw clinical conclusions at this time.