OBJECTIVES: Patients with a history of a cardiovascular (CV) disease are at high risk of developing secondary major adverse cardiac events (MACE), including death, non-fatal myocardial infarction (MI), stroke, symptomatic pulmonary embolism, CV and all-cause hospitalization, and bleeding. The objective is to review the epidemiology and burden of MACE in patients with coronary artery disease (CAD) or peripheral arterial disease (PAD) in Europe, Asia, Latin America and Canada. METHODS: A comprehensive search was conducted in PubMed, EMBASE, Cochrane and other relevant sites. 460 full-text articles, published between 2003 and 2013, were reviewed. RESULTS: MACE was more prevalent in CAD/PAD patients compared to matched controls (> 2-fold higher). Proportions of CAD patients who have had MI, stroke, or bleeding were 1.4%–3.0%, 1.24% and 0.81%, respectively. For PAD patients, these proportions were 1.37%–13.7%, 0.4%–5.2%, and 1.3%, respectively. Compared to individuals with no CV disease, MACE incidence in CAD or PAD patients was increased by at least two-fold, ranging from 18.1%–32.3% for all-cause death, 12.1%–18.9% for CV death, 8.2%–17.3% for MI and 6.8%–11.3% for stroke. In patients with CAD, evidence of MACE was reported within 30 days of primary percutaneous coronary intervention and incidence increased over time. The main risk factors for MACE in CAD/PAD patients included increased oxidative stress in coronary and peripheral arteries, diabetes, and chronic kidney disease. Limited information was found on the economic and humanistic burden of MACE in CAD/PAD patients. Available data showed that MACE occurrence increased hospitalization rates and associated costs, in addition to worsening patients’ quality of life. CONCLUSIONS: Although gaps in the literature were identified, this assessment showed that the risk of MACE is substantial among CAD/PAD patients and imposes a considerable burden. Development of preventive measures is warranted.