Given the long-term nature of methadone maintenance treatment, it is important to assess the extent of cognitive side effects. This study investigated cognitive and psychomotor performance in 51 methadone maintenance patients (MMP) as a function of time since last methadone dose and maintenance dose level. MMP maintained on doses ranging from 40 to 200 mg (mean = 97 mg) completed a battery of psychomotor and cognitive measures across 2 sessions, during peak and trough states, in a double-blind crossover design. Peak sessions were associated with worse performance on measures of sensory processing, psychomotor speed, divided attention, and working memory, compared with trough sessions. The effects of maintenance dose were mixed, with higher dose resulting in worse performance on aspects of attention and working memory, improved performance on executive function, and no effects on several measures. Longer treatment duration was associated with better performance on some measures, but was also associated with increased sensitivity to time since last dose (i.e., worse performance at peak vs. trough) on some measures. The results suggest that cognitive functioning can fluctuate as a function of time since last dose even in MMP who have been maintained on stable doses for an extended time (mean duration in treatment = 4 years), but worsened performance at peak is limited to a subset of functions and may not be clinically significant at these modest levels of behavioral effect. For patients on stable methadone maintenance doses, maintenance at higher doses may not significantly increase the risk of performance impairment.