Background Little is known about the long-term persistence and adherence of psychostimulant use in adults with attention-deficit/hyperactivity disorder (ADHD) and its relationship to their psychological well-being. Methods The persistence and adherence to psychostimulants and psychological well-being were examined in adults with ADHD in a naturalistic follow-up, starting directly after discharge from their specialized treatment of ADHD at an outpatient ADHD clinic. Ninety-six patients were included at the time of discharge, who were interviewed by telephone at 6 months, 1 year, and 3 years after discharge. Results At the time of discharge, 78% used a psychostimulant prescribed by a psychiatrist. Of those on psychostimulants at the time of discharge, approximately half still used any of these psychostimulants 3 years after discharge. However, adherence rates were good for those who persisted to use psychostimulants. The female sex and middle educational level (relative to a higher educational level) were near-significantly related to nonpersistence, and having a higher educational level and the combined ADHD subtype were related to nonadherence. In turn, nonadherence was related to worse general functioning, lower mood, and poorer sleep quality. Conclusions The importance of adherence should be discussed at the time of discharge, especially with female ADHD patients, those with a higher educational level, and those with a combined ADHD subtype, because nonadherence is associated with poorer outcomes.