Background and Purpose— Previous estimates of the prevalence of silent cerebral infarction (SCI) on MRI in community-based samples have varied between 5.8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample. Methods— Our study sample comprised 2040 Framingham Offspring (53% female; mean age, 62±9 years) who attended the sixth examination (1996–1998), underwent volumetric brain MRI (1999–2005,) and were free of clinical stroke at MRI. We examined the age- and sex-specific prevalences and the clinical correlates of SCI using multivariable logistic regression models. Results— At least 1 SCI was present in 10.7% of participants; 84% had a single lesion. SCI was largely located in the basal ganglia (52%), other subcortical (35%) areas, and cortical areas (11%). Prevalent SCI was associated with the Framingham Stroke Risk Profile score (OR, 1.27; 95% CI, 1.10–1.46); stage I hypertension was determined by JNC-7 criteria (OR,1.56; CI,1.15–2.11), an elevated plasma homocysteine in the highest quartile (OR, 2.23; CI, 1.42–3.51), atrial fibrillation (OR, 2.16; CI, 1.07–4.40), carotid stenosis >25% (OR, 1.62; 1.13–2.34), and increased carotid intimal-medial thickness above the lowest quintile (OR, 1.65; CI, 1.22–2.24). Conclusion— The prevalence and distribution of SCI in the Framingham Offspring are comparable to previous estimates. Risk factors previously associated with clinical stroke were also found to be associated with midlife SCI. Our results support current guidelines emphasizing early detection and treatment of stroke risk factors.