Résumé : Recent global data indicates a worldwide increase in polydrug use associated with a shift from recreational to productive habits of consumption. Such non-responsible abuse of substances (alcohol, cocaine, heroin, etc.) is likely to lead to addictive disorders that are characterized by various neuropsychopharmacological effects. A main cognitive function involved in the onset and long-term maintenance of addiction is reactive inhibition, i.e., the ability to withhold a prepotent motor dominant response. In the present study, 63 (poly)drug user patients who were undergoing a detoxification program, in addition to 19 healthy controls matched for gender, age, and education, were subjected to a “contextual Go/No-Go task” with concomitant electroencephalography. Stimuli were superimposed on three contextual backgrounds: control (black screen), drug-unrelated (neutral pictures), or drug-related (pictures related to drug consumption). Of these patients, 23 were cocaine users (CU), 21 were heroin users (HU), and 19 were polydrug users (PDU). The main results showed that (1) at the behavioral level, more commission errors occurred with the PDU patients compared to the healthy controls; (2) at the neurophysiological level, specific alterations were found on classical event-related potentials that index reactive inhibition. Indeed, the higher rate of errors in the PDU group was subtended by both reduced amplitude and latency on the ∆N2 component and increased ∆P3 latency compared to controls. These data clearly suggest a more deleterious impact of polydrug use on inhibitory functions. In addition, our results provide evidence of reduced ERN amplitude in cocaine users, suggesting that impaired performance monitoring and error-processing may support impaired awareness, thereby preventing these patients from changing their behaviors.