OBJECTIVES: To identify the clinical factors predicting a good clinical response to anti-TNF therapy in rheumatoid arthritis (RA) patients entered in the LORHEN registry after 5years of treatment with anti-TNF agents and divided into two groups on the basis of their baseline DAS28 scores (moderate>3.2-5.1 [MDA] and high>5.1 [HDA]). METHODS: Disease activity at baseline and after 12months was assessed using the DAS28, and response was evaluated using the EULAR improvement criteria. RESULTS: The study involved 1300 patients with established RA: 975 with HDA and 325 with MDA. After a mean 36-month, 29.6% of the patients had a DAS28 score of less or equal to 2.6 (HDA 25.8% vs. MDA 43.0%; P<0.001) and were considered to be in remission. A higher probability of a good EULAR response in patients with HDA was associated with male gender (F vs. M - OR 0.45, 95% CI 0.26-0.78; P: 0.004), lower age at the start of treatment (OR 0.98, 95% CI 0.96-0.99; P: 0.002), the absence of comorbidities (OR 0.18, 95% CI 0.06-0.52; P: 0.002) or no previous use of corticosteroids (OR 1.92, 95% CI 1.14-3.22; P: 0.015) and the use of adalimumab vs. infliximab (OR 2.21, 95% CI 1.37-3.57; P 0.001); in patients with MDA, the probability of a good EULAR response was associated with male gender (F vs. M - OR 0.39, 95% CI 0.17-0.90; P: 0.027). CONCLUSIONS: With the exception of male gender, the factors predicting a good EULAR response are different in patients with MDA and those with HDA.