OBJECTIVE: The objective of the study was to examine catastrophizing, depression and their interactive effects in predicting disability in patients with chronic pain. METHOD: A battery of questionnaires was mailed to primary care patients in a large integrated health care delivery system. The Patient Health Questionnaire was used to assess major depression, the Coping Strategies Questionnaire assessed catastrophizing and the Graded Chronic Pain Scale was used to assess pain intensity and two measures of disability, including self-report of pain interference and days missed from usual activities. Patient medical records were used to assess severe medical illness. Of the 5808 respondents, 2618 met criteria for chronic pain. Multiple regression analyses, covarying for age, gender, severe medical illness and pain intensity, estimated the main and interactive effects of catastrophic thinking and depression on two measures of pain-related disability. RESULTS: Both catastrophic thinking and depression were statistically significant predictors of both measures of pain-related disability, with larger effect sizes observed for catastrophic thinking. CONCLUSIONS: Routine assessment of both catastrophic thinking and depression is important in the treatment of chronic pain patients, and modification of these factors may reduce disability and increase the ability of chronic pain patients to participate in daily life activity.