OBJECTIVE: To examine coronary heart disease (CHD) and its risk factors as predictors of long-term trajectories of psychological distress from midlife to old age. METHODS: In the Whitehall II cohort study, 6890 participants (4814 men, 2076 women; mean age 49.5 years) had up to seven repeat assessments of psychological distress over 21 years (mean follow-up 19 years). CHD and its risk factors (lifestyle-related risk factors, diabetes, hypertension and cholesterol) were assessed at baseline. Group-based trajectory modelling was used to identify clusters of individuals with a similar pattern of psychological distress over time. RESULTS: We identified four trajectories of psychological distress over the follow-up: 'persistently low' (69% of the participants), 'persistently intermediate' (13%), 'intermediate to low' (12%) and 'persistently high' (7%). The corresponding proportions were 60%, 16%, 13% and 11% among participants with CHD; 63%, 15%, 12% and 10% among smokers and 63%, 16%, 12% and 10% among obese participants. In multivariable adjusted multinomial regression analyses comparing other trajectories to persistently low trajectory, prevalent CHD was associated with intermediate to low (OR 1.70, 95% CI 1.08 to 2.68) and persistently high (OR 1.92, 95% CI 1.16 to 3.19) trajectories. Smoking (OR 1.33, 95% CI 1.07 to 1.64; OR 1.55, 95% CI 1.19 to 2.04) and obesity (OR 1.33, 95% CI 1.04 to 1.70; OR 1.47, 95% CI 1.07 to 2.01) were associated with persistently intermediate and persistently high trajectories, respectively. CONCLUSION: CHD, smoking and obesity may have a role in the development of long-lasting psychological distress from midlife to old age.