Psoriasis is a chronic inflammatory disease. The aim of this study was to evaluate the effects of methotrexate and retinoid on risks for developing cerebrovascular disease among psoriatic patients. A population-based nested case-control study was conducted using the Taiwanese National Health Insurance database. Cox proportional hazards models were adopted. The hazard ratio (HR) of newly developed cerebrovascular disease was 1.28 (95% confidence interval (CI) = 1.162-1.413; p < 0.0001) for psoriatic vs. non-psoriatic subjects. In terms of the effects of methotrexate or retinoid on the occurrence of cerebrovascular disease, a significant protection effect (HR = 0.50; 95% CI = 0.27-0.92; p = 0.0264) was found for patients with methotrexate prescription. Retinoid prescription showed no protective effect. Further analyses revealed that a low cumulative methotrexate dose is associated with significant protective effect (HR = 0.53; 95% CI = 0.28-1.00; p = 0.0486) while a high cumulative dose was not (HR 0.80; 95% CI = 0.11-5.68; p = 0.8214). These results suggest that psoriatic patients receiving low-dose methotrexate treatment may have reduced risk for developing cerebrovascular disease. Further prospective study should be performed to validate the vasculoprotective effect of this treatment strategy.