Objective. To compare the relative safety and efficacy of auranofin (AUR), metbotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). Methods. Three hundred thirty‐five patients with active RA were entered into a 48‐week, prospective, controlled, double‐blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. Results. Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single‐drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. Conclusion. Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single‐drug treatment within the time frame of the study. Copyright © 1992 American College of Rheumatology