OBJECTIVES: To evaluate the impact of persistence with anti-tumor necrosis factor (anti-TNF) treatment on rheumatoid arthritis (RA)-related healthcare costs among RA patients. METHODS: A retrospective study, utilizing the PharMetrics managed-care claims database, was conducted. The first anti-TNF (infliximab, etanercept, or adalimumab) plus methotrexate encounter among RA patients between January 1, 2001 and January 1, 2004 was identified. Patients were required to have a minimum of 12-months of continuous plan eligibility prior to and following their index biologic date. Persistence (%) was defined as the number of days between their first biologic prescription and the last biologic encounter, divided by 365 and multiplied by 100. Two mutually exclusive cohorts were developed based on their level of anti-TNF persistence: individuals who were persistent >= 80%; and those who were persistent < 80%. RA-related costs were compared between two groups. RESULTS: A total of 1,242 patients were included, 339 patients (27.3%) with a persistency ratio < 80% and 903 (72.7%) patients with a persistency ratio >= 80%. Over two-thirds of the patients were females and the mean age was 50 years. Other than pharmacy cost, higher persistence resulted in lower non-pharmacy medical costs ($3,091versus $4,601). The higher persistence cohort had significantly lower cost in all non-pharmacy cost categories: inpatient services, physician services, other out-patient services, emergency room, and lab costs as compared to the lower persistence cohort. After adjusting for confounding variables (age, gender, co-morbidity, and disease staging), patients in the higher persistence group had a significant lower non-pharmacy cost with a lower co-morbidity. There was no difference in age, gender, and disease staging between the groups. CONCLUSION: This study indicates that while higher pharmacy costs were associated with higher persistence, non-prescription medical costs were reduced for patients who were more persistent with anti-TNFs. Future analyses need to examine the influence of higher persistence on clinical outcomes.