BACKGROUND: Current cohorts of idiopathic ventricular fibrillation (IVF) patients primarily include adult-onset patients. Underlying causes of a sudden cardiac arrest vary with age, therefore underlying causes and disease course may differ for adolescent-onset versus adult-onset patients. OBJECTIVE: To compare adolescent-onset with adult-onset patients with an initially unexplained cause for VF. METHODS: This study includes 39 patients with an index event =19 years (adolescent-onset) and 417 adult-onset patients from the Dutch Idiopathic VF registry. Event circumstances, clinical characteristics, a change in diagnosis, and arrhythmia recurrences were collected and compared between the two groups. RESULTS: In total, 42 patients received an underlying diagnosis during follow-up (median of 7 [2 - 12] years), with a similar yield (15% for adolescent-onset vs. 9% for adult-onset, p=0.16). Among the remaining unexplained patients, adolescent-onset patients (n=33) had their index event at a median age of 17 [16 - 18] years, 72% were male. The youngest patient was 13 years. In comparison with adults (n=381), adolescent-onset patients more often had their index event during exercise (p<0.01). Adolescent-onset patients experienced more appropriate implantable cardioverter defibrillator (ICD) therapy (44% vs. 26%, p=0.03) during follow-up compared with adults. Inappropriate ICD therapy (26% vs. 17%, p=0.19), ICD complications (19% vs. 14%, p=0.41) and deaths (3% vs. 4%, p=1.00) did not significantly differ between adolescent-onset and adult-onset patients. CONCLUSION: IVF may occur in adolescence. Adolescent-onset patients more often present during exercise compared with adults. Furthermore, they are more vulnerable for ventricular arrhythmias reflected by a higher incidence of appropriate ICD therapy.