Background and Purpose— It has been proposed that the deposition of the β-amyloid peptide (Aβ) in the brain parenchyma and brain blood vessels has deleterious effects. We tested the hypothesis that the levels of plasma Aβ are related to the outcome in patients with intracerebral hemorrhage. Methods— In a multicenter study, we prospectively included patients with spontaneous intracerebral hemorrhage within the first 24 hours after onset. At admission, we measured plasma Aβ40 and Aβ42 levels using ELISA techniques. Also, we recorded age, sex, vascular risk factors, National Institutes of Health Stroke Scale score, presence of intraventricular hemorrhage, localization, cause, and volume of the hematoma. We obtained the modified Rankin scale and defined a unfavorable outcome as modified Rankin scale >2 at 3 months. Bivariate and multivariate regression analyses were performed. Results— We studied 160 patients (mean age, 73.8±11.3 years; 59.4% of them were men). A favorable outcome was observed in 64 (40%) of the patients. In the bivariate analyses, unfavorable outcome was associated with high age, female sex, diabetes mellitus, presence of intraventricular hemorrhage, high blood glucose, high National Institutes of Health Stroke Scale score, high volume, and high plasma levels of Aβ42 and Aβ40. The multivariate analysis showed that increased age (odds ratio, 1.07; 95% confidence interval, 1.035–1.21; P <0.0001), high admission National Institutes of Health Stroke Scale score (odds ratio, 1.29, 95% confidence interval, 1.17–1.42; P <0.0001), presence of diabetes mellitus (odds ratio, 4.15; 95% confidence interval, 1.21–14.1; P =0.02), and Aβ42 levels >9.7 pg/mL (odds ratio, 4.11; 95% confidence interval, 1.65–10.1; P =0.02) were independently associated with an increased likelihood of an unfavorable outcome. Conclusions— High levels of plasma Aβ42 in patients with acute intracerebral hemorrhage are associated with a poor functional prognosis.