ObjectivesSeveral recent large-scale studies have indicated a prospective association between job strain and coronary heart disease, stroke and diabetes. Job strain is also associated with poorer mental health, a risk factor for cardiometabolic disease. This study investigates the prospective relationships between change in job strain, poor mental health and cardiometabolic disease, and whether poor mental health is a potential mediator of the relationship between job strain and cardiometabolic disease.MethodsWe used data from five cohort studies from Australia, Finland, Sweden and UK, including 47 757 men and women. Data on job strain across two measurements 1–5 years apart (time 1 (T1)–time 2 (T2)) were used to define increase or decrease in job strain. Poor mental health (symptoms in the top 25% of the distribution of the scales) at T2 was considered a potential mediator in relation to incident cardiometabolic disease, including cardiovascular disease and diabetes, following T2 for a mean of 5–18 years.ResultsAn increase in job strain was associated with poor mental health (HR 1.56, 95% CI 1.38 to 1.76), and a decrease in job strain was associated with lower risk in women (HR 0.70, 95% CI 0.60–0.84). However, no clear association was observed between poor mental health and incident cardiometabolic disease (HR 1.08, 95% CI 0.96–1.23), nor between increase (HR 1.01, 95% CI 0.90–1.14) and decrease (HR 1.08, 95% CI 0.96–1.22) in job strain and cardiometabolic disease.ConclusionsThe results did not support that change in job strain is a risk factor for cardiometabolic disease and yielded no support for poor mental health as a mediator.