Background: Current strategies to prevent adverse cardiovascular outcomes focus primary prevention in high-risk groups and secondary prevention in people with known cardiovascular disease. We aimed to determine the proportion of events occurring in lower-risk groups globally. Methods: We included people aged 40 years to younger than 75 years who were enrolled in the Prospective Urban Rural Epidemiology (PURE) study, which is an ongoing, international, prospective, population-based cohort study that started recruiting adults from households selected to be broadly representative of the sociodemographic composition of their communities. We prospectively documented fatal or non-fatal myocardial infarction, stroke, heart failure, or any other fatal cardiovascular event stratified by history of cardiovascular disease and by the 10-year predicted disease risk scores based on WHO 2019 laboratory risk tables (<10% [low], 10% to <20% [intermediate], and ≥20% [high]) in people without previous cardiovascular disease from 26 high-income, middle-income, and low-income countries. Outcome event rates were standardised for the cohort's age and sex distribution. Findings: Between July 11, 2000, and May 6, 2019, 128 973 participants were included from 26 countries (mean age 53·6 years [SD 8·2]; 75 858 [58·8%] were female and 53 115 [41·2%] were male). We observed 11 483 outcome events affecting 8·9% of the cohort during a median follow-up of 12·3 years (IQR 9·8–14·6). Among participants, 89 508 (69·4%) had a low cardiovascular disease risk, 22 363 (17·3%) had an intermediate cardiovascular disease risk, and 5529 (4·3%) had a high cardiovascular disease risk, while 11 573 (9·0%) had known cardiovascular disease. The age-standardised and sex-standardised cardiovascular disease incidence rates per 1000 person-years was 4·1 (95% CI 4·0–4·2) in the low-risk group, 17·7 (15·2–20·2) in the intermediate-risk group, and 40·8 (25·1–56·4) in the high-risk group. Overall, 41% of outcome events occurred in cardiovascular disease-naive participants at low risk. The proportion of adverse cardiovascular outcomes occurring in this low-risk group was inversely related to country income level (32% in high-income, 38% in middle-income, and 54% in low-income countries) and was higher in women (51%) than in men (32%). Interpretation: To achieve a substantial population-level reduction in cardiovascular disease, a fundamental change is needed, so that preventive strategies for cardiovascular disease extend beyond those at high or even intermediate predicted risk to include those at considered to be at low risk. Funding: The funding bodies are listed in the appendix (p 29).