Objective: To evaluate the efficacy, safety, and duration of action of the once-daily extended-release methylphenidate formulation PRC-063 for the treatment of ADHD in an adult laboratory classroom (ALC). Method: After dose optimization with PRC-063 over 7 weeks, adults with ADHD were randomized to 1 week of double-blind treatment with PRC-063 or placebo that ended with an ALC evaluation. The primary outcome measure was Permanent Product Measure of Performance-Total (PERMP-T) score. Results: Of 288 subjects enrolled, 221 completed the ALC visit. PERMP-T score was significantly higher for PRC-063 versus placebo at every assessment from 1 to 16 hours post-dose at the ALC visit and when averaged over 16 hours post-dose (least-squares mean difference 16.3, 95% confidence interval 7.6–24.9). The most frequent adverse events during dose optimization were headache, decreased appetite, and insomnia. Conclusion: PRC-063 provided rapid and sustained symptom relief in adults with ADHD and was well tolerated. NCT03618030.