BACKGROUND/AIMS: To evaluate the efficacy of methotrexate (MTX) treatment for the periorbital findings in adult-onset xanthogranuloma (AOX). METHODS: The medical records of three patients with AOX, with and without asthma, who were treated with MTX at Oregon Health & Science University, Portland, Oregon, USA were examined. Diagnosis of AOX was made by biopsy in all patients. The patients were evaluated between February 1998 and July 2006. All patients had failed prior medical and/or surgical treatment. MTX was administered at 10-20 mg/week with folate supplementation and a course of corticosteroids. Efficacy was assessed on the basis of improvement in skin discoloration, involvement of the visual axis and patients' report of inflammation. RESULTS: All three patients were started on MTX, but one patient discontinued treatment after 3 weeks due to nausea. With follow-up as long as 3 years, the two patients who continued treatment lost the yellow discoloration of their skin, and they reported significantly less inflammation and ptosis after treatment. Oral corticosteroids could be reduced or discontinued. CONCLUSIONS: AOX is a rare, persistent disease that commonly involves the preseptal fat. MTX is a therapeutic option for this illness.