OBJECTIVES: To characterize the cardiovascular disease (CVD) profile of individuals aged 80 and older in rural South Africa. DESIGN: First wave of population-based longitudinal cohort. SETTING: Agincourt subdistrict (Mpumalanga Province) in rural South Africa. PARTICIPANTS: Adults residents (N = 5,059). MEASUREMENTS: In-person interviews were conducted to obtain social, behavioral, economic, and clinical data. Prevalence of hypertension, diabetes, dyslipidemia, high waist-to-hip ratio, overweight and obesity, high-risk high-sensitivity C-reactive protein, smoking, stroke, myocardial infarction, angina pectoris, and heart failure in individuals younger than 65, aged 65 to 79, and aged 80 and older were compared. Associations between self-reported treatments and determinants of hypertension treatment in those aged 80 and older were assessed using multivariable regression. RESULTS: Of 5,059 individuals included, 549 (10.8%) were aged 80 and older, and their CVD prevalence was 17.9% (stroke 3.8%, myocardial infarction 0.5%, angina pectoris 13.5%, heart failure 0.7%). Hypertension prevalence in this group was 73.8%, and along with angina pectoris, it increased with age (p<.001), whereas overweight and obesity (46.4%), dyslipidemia (39.1%), and smoking prevalences (3.1%) decreased (p<.001). Hypertension treatment was significantly associated with being aged 80 and older (odds ratio (OR)=1.48; 95% confidence interval (CI)=1.14-1.92, p=.003). Male sex (OR=0.73, 95% CI=0.66-0.88, p=.001), being an immigrant (OR=0.80, 95% CI=0.65-0.98; p=.03), higher socioeconomic status (OR=1.28, 95% CI=1.06-1.53, p=.009), and higher depression score (OR=1.12, 95% CI=1.05-1.19, p<.001) were associated with hypertension treatment in those aged 80 and older. CONCLUSION: This is the first study to characterize the CVD profile of individuals aged 80 and older in sub-Saharan Africa and provides baseline data for comparison with future studies in this rapidly growing age group. J Am Geriatr Soc 66:2151-2157, 2018.