The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify "depressed patients." A total of 1875 (41.1%) were identified as "depressed patients" who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient's VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable "probability of depressed patients." Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.