© 2015 American Heart Association, Inc. Background and Purpose: There are limited data on the potential association of adherence to Mediterranean diet (MeD) with incident stroke. We sought to assess the longitudinal association between greater adherence to MeD and risk of incident stroke. Methods: We prospectively evaluated a population-based cohort of 30 239 individuals enrolled in REasons for Geographic and Racial Differences in Stroke (REGARDS) study, after excluding participants with stroke history, missing demographic data or food frequency questionnaires, and unavailable follow-up information. Adherence to MeD was categorized using MeD score. Incident stroke was adjudicated by expert panel review of medical records during a mean follow-up period of 6.5 years. Results: Incident stroke was identified in 565 participants (2.8%; 497 and 68 cases of ischemic stroke [IS] and hemorrhagic stroke, respectively) of 20 197 individuals fulfilling the inclusion criteria. High adherence to MeD (MeD score, 5-9) was associated with lower risk of incident IS in unadjusted analyses (hazard ratio, 0.83; 95% confidence interval, 0.70-1.00; P=0.046). The former association retained its significance (hazard ratio, 0.79; 95% confidence interval, 0.65-0.96; P=0.016) after adjustment for demographics, vascular risk factors, blood pressure levels, and antihypertensive medications. When MeD was evaluated as a continuous variable, a 1-point increase in MeD score was independently associated with a 5% reduction in the risk of incident IS (95% confidence interval, 0-11%). We documented no association of adherence to MeD with incident hemorrhagic stroke. There was no interaction of race (P=0.37) on the association of adherence to MeD with incident IS. Conclusions: High adherence to MeD seems to be associated with a lower risk of incident IS independent of potential confounders. Adherence to MeD is not related to the risk of incident hemorrhagic stroke.