OBJECTIVE: Rheumatoid Arthritis (RA) is a disease with high socioeconomic impact. Anti-TNF drugs have provided evidence of effectiveness in treating RA patients resistant to 2 previous conventional DMARDs, including MTX, as demonstrated by a number-needed-to-treat (NNT) of 2 to produce a 20% improvement in American College of Rheumatology (ACR) score (ACR20). Anti-TNF therapy is also costly. The aim of this retrospective longitudinal cost of care analysis was to evaluate the cost of Etanercept (ETA) vs Infliximab (IFX) used at the standard dosage (according to the ANTARES Protocol) for the treatment of RA patients after DMARDs (disease-modifying anti-rheumatic drugs) failure in Italy. METHODS: the study included subjects randomly enrolled from 7 centres participating to a prospective data collection program called ANTARES. Direct health care resources attributable to RA management (drugs, ambulatory care, day case treatments, hospitalizations) were quantified using National Health Service (NHS) tariffs expressed in Euro 2003. NHS perspective was adopted. Multiple linear regression techniques were used to investigate differences between IFX and ETA in the direct cost, adjusting for sex, age, baseline ESR (erythrocyte sedimentation rate), baseline DAS (disease activity score) and centre. RESULTS: A total of 211 (IFX 101, ETA 110) patients affected by RA (F/M 165/46; mean age 50.7 ±14.5 years old) were studied. Mean total annual direct costs for RA patients were euro 16,988 (±7,245). The regression analysis showed that adjusting for sex, baseline ESR, age, baseline DAS and centres total direct costs per patient in ETA group were 3,427 Euro lower than in IFX patients (P<0.0001). CONCLUSIONS: The total direct cost of Etanercept is statistically significantly lower than Infliximab, when the drug are used at the standard dosage, according to the ANTARES Protocol.