OBJECTIVES: To evaluate the impact of anti-tumor necrosis factor (TNF) therapy on healthcare costs in rheumatoid arthritis (RA) patients. METHODS: Two groups of patients were identified using claims data from Blue Cross Blue Shield health plans: Group A-RA patients who initiated anti-TNF therapy (adalimumab, etanercept or infliximab) between January 1, 2003 and June 30, 2005; Group B-RA patients without anti-TNF therapy. The groups were matched for gender, age and geographic region (3 controls: 1 anti-TNF user). The index date for Group A was defined as the date of first anti-TNF therapy; Group B patients were assigned the index date of their matched case. All patients were continuously enrolled for >=6 months before and >=12 months after the index date. RA-related and total healthcare expenditures, excluding anti-TNF drug cost, were calculated for the pre- and post-index periods. Multivariate analyses, controlling for potential confounders, were performed to compare per-member-per-month (PMPM) expenditures. RESULTS: In total, 9545 RA patients were included (2405 in Group A and 7140 in Group B); 70.5% were female and the average age was 48.0 years. In the pre-index period, Group A had higher RA-related PMPM ($211 versus $32, p<0.0001) and total healthcare costs ($711 versus $503, p<0.0001) than Group B. Compared with the pre-index period, RA-related PMPM costs (excluding anti-TNF drugs) decreased for Group A by $44 (-20.9%) but increased for Group B by $3 (+9.5%) (p=0.0332) during the post-index period. After adjusting for confounding variables, RA-related cost differences from pre- to post-index period remained between anti-TNF users and controls (p=0.0049). CONCLUSION: Although their pre-index RA-related costs were significantly higher, post-index RA-related costs (excluding anti-TNF drug costs) of RA anti-TNF users decreased significantly from pre-index costs compared with RA non-anti-TNF user costs. Additional analyses using clinical and quality-of-life measures are needed to determine the effectiveness of anti-TNF therapies.