BACKGROUND: Therapeutic variability not explained by patient clinical characteristics is a potential source of avoidable morbidity and mortality. We aimed to explore regional variability in the management and mortality of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: 11,931 NSTE-ACS hospital survivors enrolled in two prospective registries: EPICOR [5625 patients, 555 hospitals, 20 countries in Europe (E) and Latin America (LA), September 2010-March 2011] and EPICOR Asia (6306 patients, 218 hospitals, 8 countries, June 2011-May 2012) were compared among eight pre-defined regions: Northern E (NE), Southern E (SE), Eastern E (EE); Latin America (LA); China (CN), India (IN), South-East Asia (SA), and South Korea, Hong Kong and Singapore (KS). Patient characteristics differed between regions: mean age (lowest 59 years, IN; highest 65.9 years, SE), diabetes (21.4% NE; 35.5% IN) and smoking (32% NE; 62% IN). Variations in dual antiplatelet therapy at discharge (lowest 83.1%, IN; highest 97.5%, SA), coronary angiography (53.9% SA; 90.6% KS), percutaneous coronary intervention (35.8% SA; 78.6% KS) and coronary artery bypass graft (0.7% KS; 5.7% NE) were observed. Unadjusted 2-year mortality ranged between 3.8% in KS and 11.7% in SE. Two-year, risk-adjusted mortality rates ranged between 5.1% (95% confidence interval 2.9-7.3%) in KS to 10.5% (8.3-12.7%) in LA. CONCLUSION: Wide regional variations in patient features, hospital care, coronary revascularization and post-discharge mortality are present among patients hospitalized for NSTE-ACS. Focused regional interventions to improve the quality of care for NSTE-ACS patients are still needed.