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Objective: This study assessed the relationship between depression severity and job performance among employed primary care patients. Method: In a 2001–2004 longitudinal observational study of depression’s affect on work productivity, 286 patients with DSM-IV major depressive disorder and/or dysthymia were compared to 93 individuals with rheumatoid arthritis, a condition associated with work disability, and 193 depression-free healthy control subjects. Participants were employed at least 15 hours per week, did not plan to stop working, and had no major medical comorbidities. Measures at baseline, six, 12, and 18 months included the Work Limitations Questionnaire for work outcomes, and the Patient Health Questionnaire-9 for depression. Results: At baseline and each follow-up, the depression group had significantly greater deficits in managing mental-interpersonal, time, and output tasks, as measured by the Work Limitations Questionnaire: The rheumatoid arthritis group’s deficits in managing physical job demands surpassed those of either the depression or comparison groups. Improvements in job performance were predicted by symptom severity. However, the job performance of even the “clinically improved” subset of depressed patients remained consistently worse than the control groups. Conclusions: Multiple dimensions of job performance are impaired by depression. This impact persisted after symptoms have improved. Efforts to reduce work-impairment secondary to depression are needed.