OBJECTIVE Cortisol is associated with increased cardiovascular morbidity and mortality in patients with chronic heart failure and in the general population. The negative predictive effect of cortisol on survival in non-diabetic patients who have suffered an acute myocardial infarction (AMI) has been shown. We aimed to determine the prognostic significance of cortisol in a general group of AMI patients, as this is not well known. METHODS Plasma cortisol levels were measured in 955 consecutive patients admitted with AMI. We prospectively evaluated the relationship between cortisol and major adverse cardiovascular event (MACE), which was a composite of all-cause mortality, and combination all-cause mortality and re-hospitalization for heart failure, in post-AMI patients. RESULTS During the 2-year follow-up, MACE occurred in 261 patients (27.3%). Patients with MACE had significantly higher median levels of cortisol than those without (609.4 versus 549.4 pmol/ml, P = 0.0073). Log cortisol was independently predictive of MACE after adjusting for covariates with hazard ratio (95% confidence interval) of 1.55 (1.05-2.27), P = 0.027. Patients in the highest quartile of cortisol had significantly more risk of MACE compared with those in the lowest quartile, with an adjusted hazard ratio (95% confidence interval) of 1.91(1.16-3.15), P = 0.0120. Kaplan-Meier survival estimates for MACE were lower in patients with plasma cortisol levels in the highest quartile compared with those in the first three quartiles (Log rank test χ² for survival = 10.41, P = 0.0013). CONCLUSIONS This study has shown the prognostic significance of cortisol in 955 post-AMI patients from a single centre.