Purpose of Review: To provide an overview of recently published articles describing or applying newer methods for evaluating comparative effectiveness research (CER) in rheumatoid arthritis (RA). Recent Findings: Historically, clinical trials in RA have compared newer therapies against placebo. Newer trials designed to increase the relevance of trial results to real-world settings include head-to-head comparisons, some that incorporate noninferiority, factorial and crossover designs. Extensions of traditional meta-analysis through network meta-analysis can combine direct and indirect evidence together and can compare multiple treatments with each other.Observational data used to support CER include disease registries, administrative claims data and electronic medical records. Pooling and linking across these data sources and applying newer epidemiologic methods to analyse such data can provide more valid inferences regarding optimal treatment regimens for RA. Summary: CER methods in RA include head-to-head clinical trials, advanced techniques to summarize and aggregate data across studies, enrich the data available in observational settings and enhance the methods used for analysis. Efforts to continue to apply and improve these methodologies will address key needs of clinicians, patients and health policy decision-makers to generate evidence regarding real-world risks and benefits. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.