Stimulants used to treat attention-deficit/hyperactivity disorder (ADHD) have been well researched, but comparisons among stimulants are hindered by the absence of direct comparative trials. The goal of this work was to compare the efficacy of methylphenidate and amfetamine formulations through a meta-analysis of double-blind placebo-controlled trials. We analyzed recent published literature on the stimulant therapy of ADHD to describe the variability of drug–placebo effect sizes. A literature search was conducted to identify double-blind, placebo-controlled studies of ADHD in children and adolescents published after 1979. Meta-analysis regression assessed the influence of medication type and study design features on medication effects. Twenty-three trials met criteria and were included in this meta-analysis. These trials studied 11 drugs using 19 different outcome measures of hyperactive, inattentive, or impulsive behavior. We found significant differences between amfetamine and methylphenidate products, even after correcting for study design features that might have confounded the results. Our analyses indicate that effect sizes for amfetamine products are significantly, albeit moderately, greater than those for methylphenidate. We found that most measures of effect from all studies were statistically significant. Our findings suggest that amfetamine products may be moderately more efficacious than methylphenidate products, even after controlling for potentially confounding study design features. This difference in effect size may be due to differences between amfetamine and methylphenidate in the molecular mechanisms involved in facilitating the dopaminergic neurotransmission.