Objective. To examine the threshold in disease activity associated with switching biologic treatment regimens in rheumatoid arthritis (RA) patients in real-world clinical practice. Methods. Using data from a prospective observational North American cohort of RA patients through December 30, 2009, patients who initiated a new anti-tumor necrosis factor α (anti-TNFα) agent with ≥6 months of followup were identified. Patients were classified as switchers or maintainers depending on whether they continued their anti-TNF treatment or switched (including discontinuation) within 12 months. Level of disease activity measured by the Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints (DAS28) at the time of the switch (corresponding followup visit for maintainers) was examined and random-effect multivariable logistic regression was used to adjust for covariates. Results. Mean age and RA duration among 1,549 eligible patients were 56.1 and 9.6 years, respectively, 80% were women, 62% were initiating their first biologic, and 30% were initiating their second biologic. At the time of the switch, the median DAS28 and CDAI score were 3.1 and 8.4 among maintainers and 4.0 and 15.2 among switchers, respectively. Maintainers also experienced a greater amount of reduction in disease activity compared with switchers (CDAI:-7.7 versus-2.3, DAS28:-1.1 versus-0.3). The threshold to switch decreased over calendar time, with the greatest amount of reduction observed among patients with moderate disease activity. Conclusion. On average, physicians and patients were willing to continue biologic treatment for patients who were at or near low disease activity. The threshold to switch decreased over time, especially among partial responders. © 2011, American College of Rheumatology.