Errors in performance trigger cognitive and neural changes that are implemented to adaptively adjust to fluctuating demands. Error-related alpha suppression (ERAS)—which refers to decreased power in the alpha frequency band after an incorrect response—is thought to reflect cognitive arousal after errors. Much of this work has been correlational, however, and there are no direct investigations into its pharmacological sensitivity. In Study 1 ( n = 61), we evaluated the presence and scalp distribution of ERAS in a novel flanker task specifically developed for cross-species assessments. Using this same task in Study 2 ( n = 26), which had a placebo-controlled within-subject design, we evaluated the sensitivity of ERAS to placebo (0 mg), low (100 mg), and high (200 mg) doses of modafinil, a wakefulness promoting agent. Consistent with previous work, ERAS was maximal at parieto-occipital recording sites in both studies. In Study 2, modafinil did not have strong effects on ERAS (a significant Accuracy × Dose interaction emerged, but drug–placebo differences did not reach statistical significance after correction for multiple comparisons and was absent after controlling for accuracy rate). ERAS was correlated with accuracy rates in both studies. Thus, modafinil did not impact ERAS as hypothesized, and findings indicate ERAS may reflect an orienting response to infrequent events.