We compared medical resource use and costs among rheumatoid arthritis (RA) patients receiving alternative disease-modifying antirheumatic drugs (DMARDs). The cohort study used data from a managed care organization. Health plan members who were prescribed DMARD therapy for at least 2 consecutive months, were age 18 years or older, had at least 6 months of DMARD-free enrollment prior to the first DMARD, and had a diagnosis of RA before or during the first month of DMARD were eligible. Median duration of initial DMARD therapy was 10 months overall: 11 months for hydroxychloroquine (n = 252), 15 months for methotrexate (n = 185), 5 months for sulfasalazine (n = 49), and 5 months for other mono/combination therapy (n = 85) (p < 0.0001). The average monthly cost of care was $853, of which $294 (34%) was for RA-coded medical services. In multivariate analyses, monthly RA-coded costs varied significantly by initial DMARD. RA costs and duration of initial therapy varied significantly by initial DMARD.