We evaluated the use of quadruple evidence-based medication (EBM) combination consisting of antiplatelet therapy, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, β-blocker, and lipid-lowering agent concurrently at discharge among patients (n = 8154) with acute coronary syndrome (ACS) in 6 Middle Eastern countries. In all, 49% of the patients received the quadruple EBM combination concurrently at discharge. An adjusted model demonstrated that old age, diabetes mellitus, hyperlipidemia, hypertension, ST-segment elevation myocardial infarction, cardiac catheterization, as well as cardiologists as care providers and hospitals with cardiac catheterization facilities were all positively correlated with the use of the quadruple EBM combination. However, patients with cardiogenic shock, renal impairment, higher risk score, congestive heart failure, recurrent ischemia, and those admitted to academic hospitals were negatively correlated with the use of the quadruple EBM combination. Guideline adherence to the concurrent use of quadruple EBM combination in patients with ACS at discharge was suboptimal with wide disparity among the 6 countries.