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Background: Black race, inadequate health literacy, and poor perceived control are predictors of increased cardiovascular disease (CVD) risk. The purpose of this study was to explore the relationships among race, health literacy, perceived control, and CVD risk while controlling for known risk factors in incarcerated men. Methods: We included data from 349 incarceratedmen to examine race and CVD risk (Framingham Risk Score) using a serial mediation model with health literacy and perceived control using 95%confidence intervals (CIs) from 5000 bootstrap samples. Results: Of the participants (age, 36 ± 10; education, 12 ± 2; bodymass index, 28.3 ± 5.0), 64.2%wereWhite and 35.8%were Black. Black incarcerated men were younger (P = .047) with lower levels of health literacy (P < .001). All 3 indirect effects of race on CVD were significant, whereas the direct effect of race was not. Black incarcerated men had higher levels of CVD risk through health literacy (a1b1 = 0.3571; 95%CI, 0.0948-0.7162) and lower levels of CVD risk through perceived control (a2b2 = -0.1855; 95%CI, -0.4388 to -0.0077). Black incarceratedmen had higher levels of CVD risk through health literacy influenced by perceived control (a1b2d21 = 0.0627; 95% CI, 0.0028-0.1409), indicating that despite the protective effect of higher levels of perceived control in Black incarcerated men, CVD risk remained higher compared with their White counterparts. Conclusion: Future CVD risk reduction interventions in incarcerated men, specifically Black incarcerated men, should include goals of improving health literacy and perceived control as modifiable risk factors. [ABSTRACT FROM AUTHOR]