OBJECTIVES: Depressive symptoms are of interest after an acute coronary syndrome (ACS) due to its association with increased cardiovascular morbidity and mortality and impact on health care utilisation and costs. The objective was to analyse the psychological distress and health-related quality of life (HRQoL) of incident and recurrent ACS patients registered in the Pharmacoepidemiology General Research eXtension System (PGRx-3). METHODS: PGRx-3 comprises multi-national prospective real world datasets designed to identify risk factors of multiple diseases, describe their management and quantify the associated burdens. To this end, patients from UK, France, Italy, Germany, Spain and US are being recruited by their physicians. Information from medical records is complemented with a set of validated self-administered measures. The ACS sample for this study included 1048 patients classified according to the number of ACS events registered in their clinical records. Responses to the EQ-5D 5L ‘Anxiety/depression’ domain were used to identify moderate to extreme affectation. Bivariate tests and multivariate models to control the effect of sensitive variables (i.e age, country) were used to analyze HRQoL of ACS patients (EQ-5D VAS and index scores). RESULTS: A total of 678 patients (69.8% male, mean age-SD-=66.16-11.26-, 50.6% with non-ST elevated myocardial infarction) completed the EQ-5D (no significant differences in age or gender between responders and non-responders were found). Incident cases (n=434) were slightly younger than recurrent patients: 65.18-11.48- vs. 67.85-10.66-; p= 0.01. Moderate to extreme symptoms of anxiety/depression were reported in 17.8% of incident and 19.8% of recurrent patients (p=0.606). The presence of these emotional symptoms was not associated with the time since last ACS episode (p>0.1). Finally, adjusted EQ-5D index scores and VAS values were higher in incident patients (p< 0.05). CONCLUSIONS: A substantial presence of psychological symptoms have been highlighted in both incident and recurrent ACS patients. However, incident patients showed higher levels of HRQoL.