The aim of this study was to identify risk factors for acute surgical-site infection (SSI) after total joint arthroplasty in rheumatoid arthritis (RA) patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs). We performed a retrospective study of all consecutive total hip (THA) and total knee (TKA) arthroplasties performed during a 5-year period (THA 81; TKA 339). Multivariate logistic regression analysis was performed to identify SSI risk factors. Of the patients undergoing THA or TKA, 24 cases (5.7%) developed a superficial incisional SSI requiring the use of antibiotics and three cases (0.7%) developed an organ/space SSI necessitating surgical treatment to remove the artificial joint prosthesis. Multivariate logistic regression analysis revealed that the use of biologic DMARDs [P = 0.0007, odds ratio (OR) = 5.69; 95% confidence interval (CI) 2.07-15.61] and longer RA duration (P = 0.0003, OR = 1.09; 95% CI 1.04-1.14) were the only significant risk factors for acute SSI. Furthermore, an analysis that individually evaluated major agents (n > 10) adjusted for disease duration indicated that tumor necrosis factor alpha blockers increased the risk of SSI (infliximab P = 0.001, OR = 9.80, 95% CI 2.41-39.82; etanercept P = 0.0003, OR = 9.16, 95% CI 2.77-30.25). We found that the use of infliximab or etanercept and longer disease duration were associated with an increased risk of acute SSI in RA patients. Prospective studies are thus needed to determine the safety of biologic DMARDs in the perioperative period.