Objective: To explore dose–response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria for ADHD. Results: Nearly all participants assigned to an LDX dose achieved their assigned dose with the exception of about 4% of participants assigned to the 50 mg or 14% assigned to the 70 mg doses. Higher doses of LDX led to greater improvements in ADHD-rating scale scores, independent of prior pharmacotherapy. This was evident for both inattentive and hyperactive–impulsive symptoms. The authors found some evidence for an interaction between LDX dose and baseline severity of ADHD symptoms. Conclusion: For LDX doses between 30 and 70 mg/d, the dose–response efficacy effect for LDX is not affected by prior pharmacotherapy, but patients with a greater severity of illness may benefit more from higher doses, especially for hyperactive–impulsive symptoms. The results do not provide information about doses above 70 mg/d, which is the maximum approved dose of LDX and the highest dose studied in ADHD clinical trials.