Cognitive emotion regulation strategies are important components of cognitive-behavioral therapy (CBT). Additionally, up-regulation and difficulties in the down-regulation of negative feelings are associated with mental disorders. However, little is known about the lasting effects of cognitive emotion regulation strategies on emotional experience and associated neural activation. Therefore, this study investigated immediate and prolonged effects of emotion regulation using cognitive reappraisal and distraction on subjective report and its neural correlates. Twenty-seven healthy females took part in a 2-day functional magnetic resonance imaging study. They were instructed to either up-regulate or down-regulate their negative feelings using a situation-focused cognitive reappraisal strategy, to distract themselves by imagining a specific neutral situation, or to passively look at repeatedly presented aversive and neutral pictures. Re-exposure to the same stimuli without a regulation instruction was conducted one day later. Self-reported negative feelings and blood-oxygen-level-dependent responses served as main outcome variables. As expected, the results show successful immediate up- or down-regulation of negative feelings by cognitive reappraisal and down-regulation of negative feelings by distraction. Furthermore, these changes in negative feelings were correlated with amygdala activation. A lasting effect on emotional experience associated with stronger ventromedial prefrontal cortex activation was found for down-regulation of negative feelings via cognitive reappraisal. Compared to distraction, down-regulation via cognitive reappraisal led to reduced negative feelings and stronger dorso- and ventrolateral prefrontal cortex responses one day later. While cognitive reappraisal and distraction are both effective strategies during active regulation, only cognitive reappraisal had a lasting effect. These findings might have implications for CBT.