OBJECTIVE Functional magnetic resonance imaging research has attempted to elucidate the neurobehavioral underpinnings of cocaine dependence by evaluating differences in brain activation to cocaine and response inhibition cues between cocaine-dependent individuals and controls. This study investigated associations between task-related brain activation and cocaine use characteristics. METHODS Cross-sectional. METHODS The Center for Biomedical Imaging at the Medical University of South Carolina, USA. METHODS Fifty-one cocaine users (41 dependent). METHODS Brain activation to cocaine-cue exposure and Go No-Go tasks in six a priori selected brain regions of interest and cocaine use characteristics (i.e. cocaine dependence status, years of cocaine use, cocaine use in the past 90 days) assessed via standardized interviews. RESULTS Participants demonstrated elevated activation to cocaine (bilateral ventral striatum, dorsal caudate, amygdala) and response inhibition (bilateral anterior cingulate, insula, inferior frontal gyrus) cues in all hypothesized brain regions. Years of cocaine use was associated with task-related brain activation, with more years of cocaine use associated with greater activation to cocaine cues in right (F = 7.97, P = 0.01) and left (F = 5.47, P = 0.02) ventral striatum and greater activation to response inhibition cues in left insula (F = 5.10, P = 0.03) and inferior frontal gyrus (F = 4.12, P = 0.05) controlling for age, cocaine dependence status and cocaine use in the past 90 days. CONCLUSIONS Years of cocaine use may be more centrally related to cocaine cue and response inhibition brain activation than cocaine dependence diagnosis or amount of recent use.