Mindfulness is theorized to attenuate negative responses to stress, but the majority of prior research supporting this hypothesis has relied on cross-sectional correlations or reactions to laboratory-induced stressors. In two independent samples, we tested whether dispositional mindfulness promoted less negative reactions to naturally-occurring day-to-day stressors. Participants first completed measures of dispositional mindfulness and individual differences in negative reactivity and emotion regulation. Participants then reported their level of stress and depressed mood, at the end of each day, for 10 days. Greater daily stress was associated with increases in daily depressed mood, but the negative impact of daily stress was attenuated for people higher in dispositional mindfulness. The stress buffering effect of mindfulness was also independent of participants’ neuroticism, existing depressive symptoms, and emotion regulation tendencies. These results reveal the unique and important role dispositional mindfulness plays in producing more constructive emotional reactions to routine stress and difficulties.