OBJECTIVES: Atherothrombosis is a systemic disease associated with a high risk of cardiovascular morbidity and mortality, which represents a huge economic burden. Peripheral Arterial Disease (PAD) puts patients at a higher risk of atherothrombotic events. The aim of this study was to examine the economic impact of PAD as an added risk factor in patients with coronary artery disease (CAD) and cerebrovascular disease (CVD) using cumulative 2-year follow-up data from REACH patients from Spain. METHODS: The REACH Registry is an international registry of 67,888 patients at risk of atherothrombosis due to established CAD, CVD and/or PAD, or ≥ 3 risk factors. Cumulative 2-year rates of cardiovascular (CV) events for CV death, myocardial infarction (MI) and stroke along with their associated direct (medication and hospitalization) and indirect costs (productivity losses) were compared across patient subgroups (CAD, CVD, and/or PAD) in 2050 REACH patients. RESULTS: The 2-year CV event rates of the composite CV-death/MI/stroke/CV hospitalization for patients with CAD and CVD were 21.3% and 16.0%, respectively. Presence of symptomatic PAD as an additional risk factor increased these event rates to 30.6% and 23.3%, respectively. Cumulative 2-year vascular-related total costs were €4.747 for CAD and €3201 for CVD. These costs increased to €6205 and €5978, respectively, for patients with an additional history of symptomatic PAD. This increase in cost was due to the roughly doubling of hospitalization costs resulting from the observed higher rates of major cardiovascular events and peripheral vascular interventions and procedures (peripheral angioplasty/stenting, peripheral bypass graft, lower limb amputation) in patients with symptomatic PAD as an additional risk factor. CONCLUSIONS: CV events and hospitalization rates, and associated costs, tend to increase with the number of affected vascular beds; especially when PAD is also present in patients with CAD or CVD, compared to patients with CAD and CVD only.