Clinical experience shows that neuropsychological side effects due to opioid therapy usually decrease during the first weeks of therapy. However, the effect of long-term treatment with transdermal fentanyl on complex activities, such as driving, is not yet clear. In a prospective trial, patients with continuous noncancer pain, who had received stable doses of transdermal fentanyl for at least 2 weeks, completed a series of computerized tests to measure attention, reaction, visual orientation, motor coordination and vigilance. Data from 90 healthy volunteers were matched to 30 patients; 9 patients were excluded from the per-protocol analysis because they took additional drugs in violation of the protocol. None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls. We conclude that stable doses of transdermal fentanyl for the treatment of chronic non-cancer pain are not associated with significant impairments in psychomotor and cognitive performance. The threshold for fitness to drive as defined by German law did not differ significantly between the groups.