BACKGROUND: There are no systemic therapies approved in the United States to treat pediatric psoriasis. OBJECTIVE: We sought to evaluate long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. METHODS: This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. RESULTS: Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score ( approximately 60%-70%) and 90% improvement in Psoriasis Area and Severity Index score ( approximately 30%-40%) and static physician global assessment status clear/almost clear ( approximately 40%-50%) were maintained through week 264. LIMITATIONS: The number of patients remaining on study at week 264 was small. CONCLUSION: Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.