Stroke mortality rates differ by race and region, and smoking and exposure to secondhand smoke are associated with stroke. We evaluated regional and racial differences in current smoking and secondhand smoke exposure among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. African American and white adults (n = 26,373) aged 45 years or older were recruited during 2003 through 2007. Logistic regression was used to examine the likelihood of current smoking and secondhand smoke exposure by race (African American vs white) and region. We compared the buckle of the stroke belt (the coastal plain region of North Carolina, South Carolina, and Georgia) with the stroke belt (the remainder of North Carolina, South Carolina, and Georgia, plus Alabama, Mississippi, Tennessee, Arkansas, and Louisiana) and compared each of these regions with the remaining contiguous states. Among whites, no regional differences in current smoking were seen, but among African Americans, the odds of current smoking were 5% lower in the stroke belt, and 24% lower in the stroke buckle than those in the nonbelt region. Similarly, among whites no regional differences in exposure to secondhand smoke were found, whereas among African Americans, the odds of being exposed to secondhand smoke were 14% lower in the stroke buckle than for nonbelt residents. These data suggest that rates of current smoking and secondhand smoke exposure are not higher in regions that have higher stroke mortality and therefore cannot contribute to geographic disparities; nevertheless, given that 15% of our participants reported current smoking and 16% reported secondhand smoke exposure, continued implementation of tobacco control policies is needed.