Whether methotrexate can be safely administered during the perioperative period to rheumatoid arthritis patients undergoing arthroplasties is an issue that has not been resolved to date. We are describing our attempt to conduct a case-controlled, multicenter study addressing this issue. The estimated sample size of approximately 140 patients proved to be difficult to recruit. Complications were all mild, but there tended to be more perioperative complications in the methotrexate-treated than in the placebo-treated patients. Possible explanations for the failure to complete the study are discussed.