OBJECTIVES: Switching among tumor necrosis factor-α inhibitor (TNFi) agents or to another biologic is relatively common, but determinants of dose escalation are largely unknown. Among individuals who are escalating the dose from their first TNFi, we identified factors associated with the choice of dose escalation in a retrospective analysis of medical and pharmacy claims and eligibility data. METHODS: Eligible patients were ≥18 years of age, diagnosed with rheumatoid arthritis (RA, 2 diagnoses ≥2 months apart) from January 2003–March 2008, had initiated a new TNFi prescription after a 6-month biologic-free period and had at least 6 months of continuous enrollment. Kaplan-Meier (KM) analysis and Cox regression were used to analyze time to dose escalation. Multinomial logistic regression was used to determine factors affecting dose escalation. RESULTS: A total of 11,903 (6.9%) of 173,533 RA patients were identified. Among these patients, 16% (n=1,903) after a mean of 261 days escalated their dose.  Comorbidity scores, such as the severity index for rheumatoid arthritis (SIFRA) and Elixhauser, were higher for patients who escalated their dose. The likelihood of escalating the dose was increased by female sex, younger age, and baseline use of corticosteroids or cytotoxic agents. Baseline use of methotrexate raised the likelihood of dose escalation (relative risk ratio, 1.58). CONCLUSIONS: After initiating TNFi treatment, many RA patients failed to remain on therapy and escalated doses or switched to a second TNFi or another biologic ~1 year. Factors influencing whether patients increased their dose included gender, age, and use of certain agents at initiation of the TNFi. A limitation of this study is that patients with <6 months of TNFi treatment were not included.