ABSTRACT Objective The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA). Methods The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports. Results The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it had worsened to 7.3 ± 7.8. ACR50 response was achieved in 79.6% of patients at 3 months, 67.1% at 6 months, 79.3% at twelfth months, 70.7% at the twenty-fourth month. During ETA treatment, 10 patients required hospitalization for serious infections. Conclusion Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.