To determine the relative contribution of psychiatric comorbidity to work disability in patients with inflammatory rheumatic diseases (IRD). Parallel analyses were also performed in a matched control group with no diagnosis of IRD to investigate if predictors of work disability in medical patients are independent from the presence of IRD.The patient group with IRD (73.9% female; mean age, 42.7 years) and the control group (73.9% female; mean age, 42.2 years) consisted of 356 outpatients each. Psychiatric comorbidity was diagnosed using the Patient Health Questionnaire (PHQ), functional disability was measured with the 12-item Short-Form Health Survey (SF-12), and severity of illness was assessed by the treating physicians. Stepwise logistic regression analyses were performed to identify independent predictors of work disability controlling for psychiatric comorbidity, functional disability, severity of illness, additional clinical variables, and demographics.Psychiatric comorbidity increased work disability in patients with severe IRD from 25% to 50%, and from 5% to 17% in mild disease. Physical functioning (OR = 0.6; p <.0001), depression severity (OR = 1.6; p =.005), and illness severity (OR = 1.8; p =.006) were identified as independent predictors of work disability in patients with IRD. Similar predictors of work disability were identified in the control group, but depression severity did not meet statistical significance at the 5% level.This study provides evidence that depression is an independent risk factor of work disability in patients with IRD, but this result cannot be generalized to other medical conditions. Improved diagnosis and treatment of depressive disorders in patients with IRD may help avoid work disability.