Objective: Observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different Juvenile Idiopathic Arthritis (JIA) subtypes. Methods: At baseline we collected patient and disease characteristics of all Dutch JIA patients who started treatment with etanercept. Disease activity was evaluated (at start of the study, after three months, and then yearly) according to the JIA core set of the American College of Rheumatology Paediatric definition of improvement (ACR Pedi). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded. Results: We included 146 JIA patients with a median follow-up of 2.5 years per patient (range 0.3-7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid-factor positive, 38% polyarticular rheumatoid-factor negative, 19% oligoarticular extended, 3% enthesitis-related, and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first three months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although systemic JIA patients responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long-term. Serious adverse events rate was low (0.029 per patient-year). Conclusions: Etanercept is effective and safe in JIA, even for a great part of the systemic JIA patients. The greatest improvement occurred in the first three months of treatment, and was sustained for a long time in most patients (up to 75 months).