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Objective: Previous reports have suggested that juvenile-onset SLE is associated with a worse prognosis than adult-onset disease. There have been limited studies in adolescents. We sought to assess the effect of adolescent-onset SLE on the clinical course of a large multi-ethnic cohort., Methods: Patients consisted of individuals diagnosed with SLE between 11 and 18 years of age in a tertiary referral centre. All patients with adult-onset disease were used as controls. Data were analysed by univariable and multivariable analysis for demographic, clinical and serological data., Results: One hundred and twenty-four patients with adolescent-onset and 484 patients with adult-onset disease were identified. There was a higher percentage of males (12.9% vs 7.2%; P = 0.036) and patients of Asian ethnicity within the adolescent group (P < 0.01). By univariable analysis, adolescent-onset SLE was associated with more frequent LN and haemolytic anaemia and less serositis and SS. Ischaemic vascular events occurred in 32 adult-onset patients (6.6%) and 3 adolescent-onset patients (2.4%; P = 0.08). Thirty-five adult-onset patients developed cancer (6.8%) compared with five of the adolescent-onset group (4.8%; P = 0.54). The standardized mortality rate was significantly increased in females with adolescent-onset SLE (14.4; 95% CI 4.44, 24.4) compared with patients with adult-onset SLE. By multivariable analysis, adolescent-onset SLE retained a significant association with LN., Conclusion: Adolescent-onset SLE is associated with a significantly increased risk of LN and, importantly, with a marked increase in mortality. These data suggest a more aggressive phenotype of disease in patients with onset of SLE in adolescence and supports the need for intensive follow-up and intensive therapy in this population., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)