Since 1990 the Utrecht Rheumatoid Arthritis Cohort study group has performed several clinical trials on different treatment strategies in early rheumatoid arthritis (RA) patients. From 1990 till 1994, patients were randomly assigned to the pyramid strategy group or the early DMARD group. Patients in the early DMARD group were allocated to one of the three following treatment strategies: strategy I, starting with hydroxychloroquine (HCQ); strategy II, starting with intramuscular gold (iAU); or strategy III, starting with oral methotrexate (MTX). After one year, statistically significant advantages for the early DMARD group compared with the pyramid group were found for disability, pain, joint score, and ESR. The increase in radiological damage did not differ significantly between the two strategy groups. These first year results proved that early introduction of DMARDs is more beneficial than a delayed introduction. After 5 years, however, no prolongation of the clinical advantages in favor of the early DMARD group, as observed after one year, was found. It was found that patients assigned to the pyramid group received more intra-articular injections during the first two years; at the end of this period 75% of them used DMARDs, especially the more aggressive DMARDs. Based on the first year results, all patients were randomly assigned to one of the three treatment strategies in the early DMARD group between 1994 and 1998. Patients who started with MTX or iAU as the first DMARD demonstrated better results regarding clinical efficacy and radiological damage after 2 years. However, more patients who received iAU therapy had to discontinue their therapy compared with patients who took MTX. We therefore conclude that MTX is the DMARD of first choice and that treatment should be tailored to the individual patient.