A three-year open-label study of atomoxetine in adults with ADHD followed two multicenter, double-blind trials. In the double-blind trials, female gender and higher levels of emotional symptoms were associated with better outcome. Following a 4-week placebo washout period, 384 (of 536) subjects continued into the open-label study. 61% of subjects entering this open-label study remained after 6 months at an average dose of 100 mg/day. Subjects who had previously responded to double-blind atomoxetine achieved maximum response after 8 weeks of open-label medication, but others continued to improve for 36 weeks. Women improved more (7.7 ± 6.4) than men (6.1 ± 6.4) on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) (P = .007) and the Conners' Adult ADHD Rating Scale (P = .03). Subjects with emotional dysregulation improved more than others on the WRAADDS (P = .001). Responders ultimately improved approximately 60% in attentional, hyperactive/impulsive, and emotional symptoms. Thirty-nine percent of atomoxetine double-blind non-responders became responders during open-label treatment.