The stress-reductive effect of mindfulness practice is well-established, yet less is known about the cognitive mechanisms underlying this salutary outcome. We conducted a prospective observational study of 339 participants (mean age 45.7 ± 13.4) undergoing an 8-week mindfulness-based stress and pain management course and found support for our hypotheses that a) pre-post intervention increases in dispositional mindfulness are reciprocally linked with increases in positive reappraisal coping and b) the stress-reductive effects of increases in dispositional mindfulness are mediated by increases in positive reappraisal independent of changes in catastrophizing. Positive reappraisal and mindfulness appear to serially and mutually enhance one another, creating the dynamics of an upward spiral. Through mindfulness practice, individuals may engender a broadened state of awareness that facilitates empowering interpretations of stressful life events, leading to substantially reduced distress. Study findings have implications for cognitive therapy that couples mindfulness practices with restructuring techniques oriented toward benefit finding and positive reappraisal.