To determine the frequency, location, size, and risk factors for silent cerebral infarctions (SCIs) on brain CT, we identified 629 patients without a history of previous stroke who were enrolled in a multicenter clinical trial of therapy for acute ischemic stroke. On the baseline CT, 143 patients (22.7%) had SCIs; 34.3% of the lesions were in the right hemisphere, 38.5% in the left hemisphere, and 27.3% were bilateral. The lesion size was < 1 cm in 65.7%, and the most common site was the basal ganglia (48.3%). Patients with SCI were compared with controls without SCI to determine the odds ratios (ORs) for each risk factor. On univariate analysis, race (black versus white) had an OR of 1.80 (95% confidence interval [CI], 1.14 to 2.85), male sex an OR of 1.68 (95% CI, 1.12 to 2.51), and congestive heart failure an OR of 1.88 (95% CI, 1.07 to 3.31). Significant risk factors on multivariate analysis include age (OR 1.03 per year, p = 0.0070), male sex (OR 1.78, p = 0.0094), and race (OR 2.43, p = 0.0004). After including interaction terms with age and hypertension and age, sex, and race, hypertension was also a significant risk factor.