Background: Sense of Coherence (SOC) is a measure of an individual's capacity to use various coping mechanisms and resources when faced with a stressor. Chronic pain is one of the most prevalent and disabling conditions in clinical practice. This study examines the extent to which a strong SOC is associated with less pain and better health related quality of life (HRQoL) among patients with chronic pain.Methods: We analyzed data from the Stepped Care to Optimize Pain care Effectiveness (SCOPE) trial which enrolled 250 patients with persistent (3 months or longer) musculoskeletal pain who were receiving care in an United States Department of Veterans Affairs (VA) primary care clinic. The abbreviated three-item SOC scale was used to measure personal coping capability. Participants were categorized into Strong SOC (score 0-1) and Weak SOC (score 2-6). The Brief Pain Inventory (BPI) was used to assess the severity and disability associated with pain. Additionally, pain self-efficacy (ASES) and catastrophizing (CSQ) were assessed. HRQoL was assessed with the 36-item Short-Form Health Survey (SF-36) social functioning, vitality, and general health subscales. Multiple linear regression models were performed to examine whether SOC was independently associated with pain-specific and HRQoL outcomes, after adjusting for sociodemographic and socioeconomic characteristics, medical comorbidities and major depression.Results: Of the 250 study patients, 61% had a strong SOC whereas 39% had a weak SOC. Multivariable linear regression analysis showed that a strong SOC was significantly associated with better general health, vitality, social functioning and pain self-efficacy as well as less pain catastrophizing. These significant findings were partially attenuated, but remained statistically significant, after controlling for major depression. SOC was not significantly associated with pain severity or pain disability.Conclusions: A strong SOC is associated with better HRQoL and self-efficacy as well as less catastrophizing in patients with chronic pain. SOC may be an important coping mechanism (strategy) for patients with chronic musculoskeletal pain.Trial registration: Clinicaltrials.gov Identifier: NCT00926588.