Background: While the effect of psychological stress and depression on the course of heart disease is commonly recognized, the relationship between recent life events, major depression, depressive symptomatology and the onset of acute coronary heart disease (CHD) has been less considered. The aim of this study was to investigate the presence of stressful life events, major and minor depression, recurrent depression and demoralization in the year preceding the occurrence of a first acute myocardial infarction (AMI) and/or a first episode of instable angina and to compare stressful life events, also related with mood disorders, in patients and healthy controls. Methods: 97 consecutive patients with a first episode of CHD (91 with AMI and 6 with instable angina) and 97 healthy subjects matched for sociodemographic variables were included. All patients were interviewed with Paykel’s Interview for Recent Life Events, a semistructured interview for determining the psychiatric diagnosis of mood disorders (DSM-IV), a semistructured interview for demoralization (DCPR). Patients were assessed while on remission from the acute phase. The time period considered was the year preceding the first episode of CHD and the year before the interview for controls. Results: Patients with acute CHD reported significantly more life events than control subjects (p < 0.001). All categories of events (except entrance events) were significantly more frequent. 30% of patients were identified as suffering from a major depressive disorder; 9% of patients were suffering from minor depression, 20% from demoralization. Even though there was an overlap between major depression and demoralization (12%), 17% of patients with major depression were not classified as demoralized and 7% of patients with demoralization did not satisfy the criteria for major depression. Independently of mood disorders, patients had a higher (p < 0.001) mean number of life events than controls. With regard to life events, the same significant difference (p < 0.001) compared to controls applied to patients with and without mood disorders. Conclusions: Our findings emphasize, by means of reliable methodology, the relationship between life events and AMI. These data, together with those regarding traditional cardiac risk factors, may have clinical and prognostic implications to be verified in longitudinal studies.