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Abstract: The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18–60) with chronic fatigue syndrome (CFS). The study's primary outcome measure was the Behavior Rating Inventory of Executive Function—Adult (BRIEF—A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning. Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70mg/day) of either placebo or LDX for a 6-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF—A scores (M change =21.38, SD=15.85) than those in the placebo group (M change =3.36, SD=7.26). Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed. [Copyright &y& Elsevier]