In developing policies for use of expensive agents, such as those used for the treatment of rheumatoid arthritis, managed care organizations have invoked “stepped care,” in which physicians and patients must first try more established and less costly agents. N-of-1 clinical trials are multiple crossover trials in a single patient. In this cost-minimization analysis, we show that offering patients with rheumatoid arthritis the opportunity to participate in an n-of-1 trial comparing methotrexate with etanercept could save costs relative to open access while preserving clinical freedom relative to mandatory stepped care. In the primary model, the n-of-1 trial option was 15% more expensive than stepped care but 47% cheaper than open access to etanercept. More research is needed on the acceptability, safety, and generalizability of this promising approach.