Objective: To investigate the prevalence and severity of fatigue in adolescents and young adults with acquired brain injury (ABI) compared with healthy controls (HCs) and to examine associations between fatigue and gender, age and level of education. Methods: This cross-sectional study included 15-30 year old patients with ABI and a convenience sample of 15-30 year old HCs. All participants completed the 20-item Multidimensional Fatigue Inventory (MFI-20). Pathological fatigue was defined as "General Fatigue" ?12. Adjusted mean differences between groups were calculated using multivariate analysis of covariance (MANCOVA). The adjusted prevalence proportion ratio (PPRadj) of pathological fatigue was calculated using Poisson regression. Results: The patients (n?=?334) had higher scores than the HCs (n?=?168) on all MFI-20 subscales with adjusted mean differences ranging from 1.7 to 4.7 and a higher prevalence of pathological fatigue (73% versus 29%), PPRadj 2.7 (95% confidence interval 2.1-3.5). Female patients experienced more fatigue than males on the "General Fatigue" and "Reduced Activity" subscales, while no gender differences were found in the HC group. Patients and HCs with elementary education had elevated scores on the "Reduced Activity" and "Mental Fatigue" subscales. Age was not associated with any of the subscale scores. Conclusion: Young patients with ABI had markedly higher prevalence and severity of fatigue than HCs. Age (15-30 years) was not associated with fatigue. No clear patterns of associations were evident with gender and level of education. Abbreviations: ABI: acquired brain injury; CI: confidence interval; GF: general fatigue; GOSE: Glasgow Outcome Scale Extended; HC: healthy control; MANCOVA: multivariate analysis of covariance; MF: mental fatigue; MFI-20: Multidimensional Fatigue Inventory-20; PF: physical fatigue; RA: reduced activity; RM: reduced motivation; TBI: traumatic brain injury.