OBJECTIVES: This study estimated the relationship between job stress and unemployment through a 2-year follow-up study in the KOSS cohort. METHODS: We established the KOSS cohort in 2004. Among this cohort, we selected 5680 persons with complete KOSS scores and resident registration numbers. We investigated the state of unemployment using unemployment insurance data from Jan. 2005 to Oct. 2006. Multiple logistic regression analysis was performed to evaluate the relationship between job stress and unemployment. We also adjusted for age, education, marital status, experience of medical visiting, and size of enterprise. RESULTS: Insufficient job control, interpersonal conflict, job insecurity, occupational system, and lack of reward were related to unemployment for men, while only lack of reward was an unemployment risk factor for women. CONCLUSIONS: Insufficient job control, interpersonal conflict, job insecurity, occupational system, and lack of reward were found to be risk factors for male unemployment. Efforts should be made to reduce these job stressors as risk factors.