BACKGROUND: Studies report a protective effect of higher attained educational level (AEL) on cardiovascular outcomes. However, most of these studies have been conducted in high-income countries (HICs) and lack representation from low- and middle-income countries (LMICs), which bear >80% of the global burden of cardiovascular disease. METHODS AND RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry is a prospective study of 67 888 subjects with either established atherothrombotic (coronary, cerebrovascular, and/or peripheral arterial) disease or multiple atherothrombotic risk factors enrolled from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9 to 12 years, trade or technical school, and university) was self-reported for 61 332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk factors and the rate of incident cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL groups, stratified by sex and world region (LMICs or HICs). Educational attainment was inversely associated with age and diabetes mellitus and directly associated with hypercholesterolemia in all subjects. However, for other risk factors such as obesity, smoking, hypertension, and baseline burden of vascular disease, AEL was protective (inversely associated) in HICs but not protective in LMICs. The protective effect of greater AEL on incident cardiovascular events was strongest in men from HICs (P<0.0001), more modest in women from HICs (P=0.0026) and in men from LMICs (P=0.082), and essentially absent in women from LMICs (P=0.32). CONCLUSION: In contrast to HICs, higher AEL may not be protective against cardiovascular events in LMICs, particularly in women.