OBJECTIVE To test whether psychological distress and personality variables mediate or moderate physical health-related quality of life (HRQOL) in rheumatoid arthritis (RA) patients. METHODS In 168 RA patients the following self-report instruments were administered: the Health Assessment Questionnaire (HAQ), the General Health Questionnaire (GHQ), the Defence Style Questionnaire (DSQ), the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Sense of Coherence (SOC) scale. A total of 152 patients with several rheumatological disorders [56 with systemic sclerosis (SSc), 56 with systemic lupus erythematosus (SLE) and 40 with Sjögren's syndrome (SS)] served as disease controls. The outcome measure was the physical scale of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF). We used hierarchical regression to determine whether our data were consistent with the disablement process model. RESULTS In RA patients, sense of coherence was associated with physical HRQOL but the relationship was mediated by psychological distress. Self-sacrificing defence style moderated the relationship between pain and physical HRQOL: pain was associated with impaired physical HRQOL only in patients with predominant self-sacrificing defence style. Although psychological distress and personality variables were also associated with physical HRQOL in the disease control group, the moderating effects of personality on physical HRQOL were unique to RA. Thus, in RA, psychological distress, functional disability, and the interaction term between pain and self-sacrificing defence style were independently associated with physical HRQOL. CONCLUSIONS In RA patients, psychological distress mediated the association of personality variables with physical HRQOL but personality moderated the effects of pain on physical HRQOL and this could be relevant to psychological interventions.