Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs.