Objective: To investigate associations of work-related stressors and their changes over time with the risk of developing metabolic syndrome (MetS) among Japanese manufacturing workers. Methods: Participants were 1,040 employees aged 19 to 68 years who were free from MetS at baseline and completed the three year-interval follow-up survey. MetS was defined according to the Joint Interim Statement. Work-related stressors (job strain, job demands, job control, and worksite social support) were assessed based on the Job Content Questionnaire and were split into two categories (low and high) by the median value at each survey. Multivariable logistic regression was performed to investigate the associations of baseline work-related stressors and their changes over time with the incidence of MetS. Results: Three years later, 61 workers developed MetS. Higher job demands at baseline were significantly associated with a lower risk of MetS (adjusted odds ratio 0.46, 95% confidential interval: 0.24, 0.89). In the analyses of the changes in stressors over time, those whose job demands changed from low to high showed significantly higher risk of MetS (adjusted odds ratio 3.27, 95% confidential interval: 1.46, 7.34), compared with those who reported low job demands in both surveys. Conclusions: Results suggest that an increase in job demands over time, but not higher job demands at baseline, is associated with increased risk of MetS.