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Background: Cerebrovascular disease is common in Alzheimer’s disease (AD). Elevated plasma homocysteine (pHcy) levels are reported to be associated with an increased risk of poor cognition and dementia. Objective: To determine whether high pHcy levels are associated with an increased risk of coexisting silent brain infarctions (SBIs) in AD. Methods: Study population comprising 143 outpatients with clinical diagnosis of probable AD (73.3 ± 7.0 years) were classified into 2 groups according to the presence or absence of SBIs on magnetic resonance imaging. Results: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy levels in the AD with SBIs (14.0 ± 4.5 µmol/l) were significant ly elevated compared with the AD without SBIs (11.7 ± 4.7 µmol/l, p = 0.007). After adjusting for age and gender, high pHcy (>12.4 µmol/l), but not hypertension, was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI = 1.74–12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal tau or amyloid β-peptide_1–42 levels were not significantly correlated with pHcy levels in AD. Conclusion: SBIs commonly coexist with AD, and may be a unique vascular condition in which homocysteine plays an important role. Homocysteine-lowering therapy rather than antihypertensive medication might be an appropriate strategy to prevent stroke associated with AD.