The contribution of the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), to cognitive control remains controversial. Here, we examined whether the rostral ACC is necessary for reactive adjustments in cognitive control following the occurrence of response conflict [Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. Conflict monitoring and cognitive control. Psychological Review, 108, 624–652, 2001]. To this end, we assessed 8 patients with focal lesions involving the rostral sector of the ACC (rACC patients), 6 patients with lesions outside the frontal cortex (non-FC patients), and 11 healthy subjects on a variant of the Simon task in which levels of conflict were manipulated on a trial-by-trial basis. More specifically, we compared Simon effects (i.e., the difference in performance between congruent and incongruent trials) on trials that were preceded by high-conflict (i.e., incongruent) trials with those on trials that were preceded by low-conflict (i.e., congruent) trials. Normal controls and non-FC patients showed a reduction of the Simon effect when the preceding trial was incongruent, suggestive of an increase in cognitive control in response to the occurrence of response conflict. In contrast, rACC patients attained comparable Simon effects following congruent and incongruent events, indicating a failure to modulate their performance depending on the conflict level generated by the preceding trial. Furthermore, damage to the rostral ACC impaired the posterror slowing, a further behavioral phenomenon indicating reactive adjustments in cognitive control. These results provide insights into the functional organization of the medial prefrontal cortex in humans and its role in the dynamic regulation of cognitive control.