Pulse pressure (PP) has been associated with atrial fibrillation (AF) independent of other measures of arterial pressure and other AF risk factors. However, the impact of gender, race, age, and geographic region on the association between PP and AF is unclear. A cross-sectional study of data from 25,109 participants (65 ± 9 years, 54% women, 40% black) from the Reasons for Geographic and Racial Differences in Stroke study recruited between 2003 and 2007 were analyzed. AF was defined as a self-reported history of a previous physician diagnosis or presence of AF on ECG. Multivariable logistic regression models were used to calculate the odds ratio for AF. Interactions for age (<75 years and ≥75 years), gender, race, and region were examined in the multivariable adjusted model. The prevalence of AF increased with widening PP (7.9%, 7.9%, 8.4%, and 11.6%, for PP < 45, 45-54.9, 55-64.9, and ≥65 mm Hg, respectively, [P for trend <.001]) but attenuated with adjustment. No differences by gender, race, and region were observed. However, there was evidence of significant effect modification by age (interaction P = .0002). For those <75 years, PP ≥ 65 mm Hg compared to PP < 45 mm Hg was significantly associated with higher risk of AF in both the unadjusted and multivariable adjusted models (odds ratio = 1.66 [95% CI = 1.42-1.94] and 1.32 [95% CI = 1.03-1.70], respectively). In contrast, higher PP (55-64.9 mm Hg) among those ≥75 years was significantly associated with a lower risk of AF. The relationship between PP and AF may differ for older versus younger individuals.