Abstract Background We examined the association between annual changes in job strain and incident coronary heart disease (CHD) in a population-based cohort study in Denmark. Methods We studied all workers residing in Denmark in 2000, aged 30-59 years with no prevalent CHD (N = 1,660,150). Using a job exposure matrix (JEM) with annual updates, we assessed changes in job strain from 2000-2009. Incident CHD was identified in hospital and death registers from 2001 to 2010. Using Cox regression, we calculated hazard ratios (HR) and 95% confidence intervals (CI) for the association between annual changes in job strain and incident CHD. Results During 16.1 million person-years (mean time of follow-up: 9.7 years), we identified 24,159 CHD cases (15.0 per 10,000 person-years). Compared to persistent no job strain, persistent job strain (HR 1.07, 95% CI 1.03–1.10), onset of job strain (HR 1.20, 95% CI 1.12–1.29) and removal of job strain (HR 1.20, 95% CI 1.12–1.28) were associated with higher CHD incidence. Conclusions Persistent and onset of job strain was associated with a higher risk of CHD. Removal of job strain was also associated with a higher risk, which might be due to health selection. Our results suggest that job strain contributes to risk of CHD in the Danish workforce. Key messages Implementing JEM in a population-based cohort of more than 1.6 million workers enabled us to demonstrate associations between annual changes in job strain and risk of incident CHD.