BACKGROUND: The atherosclerosis cardiovascular disease (ASCVD) Pooled Cohort risk equations have shown different calibration across US populations with varied levels of social deprivation. METHODS AND RESULTS: We analyzed the calibration and discrimination of the Pooled Cohort risk equations by social deprivation status among 9066 REGARDS (REasons for Geographic And Racial Differences in Stroke) study participants not taking statins for whom ASCVD risk may lead to statin initiation. Patients were aged 45 to 79 years, had no ASCVD or diabetes mellitus, and had a low-density lipoprotein cholesterol level 70 to 189 mg/dL. Social deprivation was defined using 3 indicators: annual household income <$25 000, less than a high school education, and living without a partner. At baseline in 2003-2007, 54.6%, 27.4%, and 18.0% of participants had 0, 1, and 2 or 3 indicators showing deprivation, respectively. From baseline through December 2012, 457 participants developed ASCVD (nonfatal/fatal stroke, myocardial infarction, or coronary heart disease death). Predicted and observed ASCVD incidence per 1000 person-years were 8.02 and 6.23 (95% CI, 5.31-7.31), respectively, among participants with 0 indicators of deprivation (Hosmer-Lemeshow P=0.01); 8.05 and 6.61 (95% CI, 5.29-8.24), respectively, with 1 indicator (P=0.09); and 9.83 and 11.40 (95% CI, 9.23-14.05), respectively, with 2 or 3 indicators (P=0.12). The C-index (95% CI) was 0.72 (0.69-0.75), 0.73 (0.69-0.78), and 0.70 (0.65-0.75) among participants with 0, 1, and 2 or 3 indicators of deprivation, respectively. The net reclassification improvement after adding deprivation data to the Pooled Cohort risk equations was modest (0.12; 95% CI, 0.03-0.21). CONCLUSIONS: The Pooled Cohort risk equations have good calibration among individuals with social deprivation but overestimate ASCVD risk among those with less social deprivation.