Objective This study compared changes in bodily pain, health-related quality of life (HRQoL), and psychological symptoms during an 8-week mindfulness-based stress reduction (MBSR) program among groups of participants with different chronic pain conditions. Methods From 1997-2003, a longitudinal investigation of chronic pain patients ( n=133) was nested within a larger prospective cohort study of heterogeneous patients participating in MBSR at a university-based Integrative Medicine center. Measures included the Short-Form 36 Health Survey and Symptom Checklist-90-Revised. Paired t tests were used to compare pre–post changes on outcome measures. Differences in treatment effect sizes were compared as a function of chronic pain condition. Correlations were examined between outcome parameters and home meditation practice. Results Outcomes differed in significance and magnitude across common chronic pain conditions. Diagnostic subgroups of patients with arthritis, back/neck pain, or two or more comorbid pain conditions demonstrated a significant change in pain intensity and functional limitations due to pain following MBSR. Participants with arthritis showed the largest treatment effects for HRQoL and psychological distress. Patients with chronic headache/migraine experienced the smallest improvement in pain and HRQoL. Patients with fibromyalgia had the smallest improvement in psychological distress. Greater home meditation practice was associated with improvement on several outcome measures, including overall psychological distress, somatization symptoms, and self-rated health, but not pain and other quality of life scales. Conclusion MBSR treatment effects on pain, HRQoL and psychological well-being vary as a function of chronic pain condition and compliance with home meditation practice.