The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Plasma total homocysteine (tHcy), which increases with diabetes, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of WML correlates with tHcy in rheumatoid arthritis patients. Based on brain magnetic resonance imaging findings, 65 rheumatoid arthritis patients were divided into 2 groups: WML-positive group (61 ± 6 years, mean ± SD; n = 25) and WML-negative group (60 ± 7 years, n = 40). The level of metabolic parameters was assessed by total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and homocysteine (tHcy). The duration of rheumatoid arthritis was longer in the WML-positive group than in the WML-negative group (P < .05). Plasma levels of triglyceride was higher whereas high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < .05 and P < .01, respectively). Fasting plasma glucose (P < .05) and tHcy (<.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the tHcy (odds ratio, 1.35; 95% confidence interval, 1.12-1.63; P < .0001). Our findings indicate that the presence of WML was associated with the tHcy in Japanese patients with rheumatoid arthritis.