Etanercept is approved for the treatment of patients with juvenile idiopathic arthritis (JIA) above the age of 2 years. Experience with younger children is limited. The aim of the present study was to evaluate the efficacy and safety of treatment with etanercept in children with JIA younger than 2 years. The prospective long-term observational BIKER registry documents baseline demographics, clinical characteristics, disease activity parameters and safety issues. Efficacy was determined using the PedACR response criteria, the JADAS-10 and the proposed criteria for inactive disease and remission after 3, 6, 12, 18 and 24 months. Safety assessments were based on adverse events (AE) and serious adverse events (SAEs) reports. Between January 2001 and June 2013, a total of 13 patients including four patients with systemic JIA (sJIA), four patients with extended oligoarthritis, one patient with persistent oligoarthritis and four patients with RF negative polyarthritis were treated with etanercept. Eleven patients with follow-up assessments were analysed in our study. Prior to etanercept, all patients have been exposed to methotrexate. At last observation, 6/11 patients reached a PedACR 70 response. Two patients with sJIA and 1 with nonsystemic JIA achieved inactive disease. Tolerability was good in most of the patients. Eight AE and one SAE occurred. One patient with sJIA was affected by Hodgkin's disease 18 months after discontinuation of etanercept. New onset uveitis occurred in two patients. Reasons for discontinuation were inefficacy in three (2 sJIA), intolerance in two, remission in three (2 sJIA) and the parents' request in one patient. Etanercept seems to improve JIA patients younger than 2 years including some of the patients with sJIA. Attention should be paid to the development of malignancies and autoimmune disorders.