To determine if methotrexate (MTX) contributes to early postoperative complications, we studied 38 patients with rheumatoid arthritis (RA) who underwent elective orthopedic surgery. There were 4 complications of prosthetic joint infection or wound dehiscence or infection among 19 procedures performed on patients who continued MTX until < 4 weeks before surgery, compared to no complications among 34 procedures performed on patients who discontinued MTX 4 weeks before surgery or who were taking no remittive agent for 3 months before surgery (p < 0.03, Fisher's exact, 2-tailed). No demographic, clinical, laboratory, nutritional, or intraoperative differences between the 2 groups were apparent, suggesting that MTX may play a role in early postoperative complications in patients with RA. A larger, prospective trial to study this issue is warranted.