Cognitive impairment in drug-dependent patients receiving methadone maintenance treatment has been reported previously, although the literature is limited and results remain controversial. Long-term effects under stable methadone maintenance treatment (MMT) and the possibility of improvement in cognitive performance during long-term substitution treatment have rarely been investigated. We performed a comparative study investigating differences in cognitive functions under short- and long-term methadone treatment to test the hypothesis that patients perform better under long- than under short-term MMT. Seventy-seven patients were assessed cross-sectional either at least 30 days after the start of MMT (short-term group, n=35) or after at least 6 months of MMT (long-term group, n=42) with a comprehensive neuropsychological test battery on intelligence, learning and memory, attention and executive functions. Urine screenings were performed immediately before neuropsychological testing to check for concomitant drug use. Our findings may suggest, with all due caution, a slightly better performance of the long-term group in executive functions and visuo-construction. No group differences were found in attentional functions and learning and memory. More longitudinal research and studies controlling for the effects of dosage and duration of opioid addiction are necessary to examine whether cognitive ability may improve under long-term MMT.