Using fMRI, we investigated the behavioral and neural consequences of Compassion meditation when employed as an emotion regulation strategy and compared this to Reappraisal based cognitive emotion regulation. 15 expert meditators were scanned while either passively viewing, or using Compassion meditation or Reappraisal to regulate their emotional reactions to short film clips depicting people in distress. Subjective affect ratings showed that Compassion meditation primarily increased positive affect while Reappraisal primarily decreased negative affect. Neuroimaging results showed that the Compassion vs. Passive Viewing contrast was associated with increased activation in regions involved in affiliation and positive affect (ventral striatum, mOFC), in addition to cognitive (left IFG, TPJ, pre-SMA) and affective (sgACC) control regions. Mirroring behavioral results, the Compassion vs Reappraisal contrast showed higher activation in regions involved in negative (amygdala, insula) and positive (ventral striatum, mOFC) affect and emotional control regions (sgACC). Relatively lower activation was observed in cognitive control regions (Frontoparietal network, IFG). Our findings demonstrate the efficacy of Compassion meditation as an emotion regulation strategy, suggesting that the active regulatory mechanism of Compassion is primarily the up-regulation of positive affect. Thus, Compassion is markedly different from other coping strategies in relying less on cognitive effort when faced with stressors, suggesting it could be powerful strategy for the fostering of resilience.