Copyright © 2014 by the American College of Rheumatology Objective: To examine the patterns of methotrexate (MTX) use among rheumatoid arthritis (RA) patients. Methods: Using data from RA patients enrolled in a US commercial health plan and the US Medicare program, we identified RA patients initiating oral MTX. Persistence with MTX (oral or subcutaneous [SC]) was defined as no gap for ≥90 days. Results: New oral MTX users in Medicare (n = 20,431) were 76.9% women, had a mean ± SD age of 69.7 ± 11.7 years, and contributed a median followup of 2.6 years (interquartile range 1.7–3.5 years). Only 38% received dosages ≥20 mg/week at any time. Approximately 50% of patients discontinued MTX at 1 year, although more than one-third of patients subsequently restarted. New commercially insured oral MTX users (n = 4,048) were similar to Medicare patients, except for age. Among Medicare patients, 19% starting oral MTX subsequently initiated a biologic agent, mostly anti–tumor necrosis factor (85%). Of these, only 50% received MTX at a dosage of ≥20 mg/week, and only 21% of individuals switched to SC MTX (4%) or received hydroxychloroquine (8%), sulfasalazine (5%), or leflunomide (8%) prior to biologic agents. In commercially insured patients, 35% initiated a biologic agent, mostly anti–tumor necrosis factor therapies (90%). Of these, 43% never received MTX ≥20 mg/week. Conclusion: Titration to a higher-dose oral MTX and use of SC MTX among RA patients were infrequent and may have been underutilized. Further work to optimize MTX dosing before patients are switched to a biologic agent may be warranted.