The regulation of negative emotion through reappraisal has been shown to induce increased prefrontal activity and decreased amygdala activity. Individual differences in dispositional mindfulness reflect differences in typical recognition, detachment and regulation of current experience, thought to also operate as top-down control mechanism. We sought to investigate whether such individual differences would be associated with brain activity elicited during reappraisal of negative emotion. Eighteen healthy participants completed a functional magnetic resonance imaging task that involved attending to or reappraising negative stimuli, and provided emotion experience ratings after each trial. Dispositional mindfulness was assessed with a self-report questionnaire. Reappraisal induced activity in a brain network involving predominantly dorsal portions of the prefrontal cortex, replicating previous studies. A voxelwise regression analysis showed that individual differences in the tendency to be mindful predicted activity in neural regions underlying reappraisal, with dorsomedial prefrontal cortex activation increasing with more mindfulness traits. Notably, this prefrontal activation was inversely correlated with the amygdala response to negative scenes, further supporting its role in down-regulating emotion-generation regions. These findings suggest that individual differences in dispositional mindfulness, which reflect the tendency to recognize and regulate current states, may modulate activity in neural systems involved in the effective cognitive control of negative emotion.