Background: Little is known about the prevalence of emotional difficulties and self-harm among adolescents with a disability. Objective: Our aims were: (1) to estimate the prevalence of emotional difficulties and self-harm among British adolescents with and without disability; (2) to determine whether prevalence varies by gender, severity of disability and type of functional limitation associated with disability. Methods: Secondary analysis of age 14 data from the UK's Millennium Cohort Study. Results: Adolescents with disability reported significantly higher rates of emotional difficulties and self-harm than their non-disabled peers. Among participants with and without disability, prevalence rates were notably higher among girls for most outcomes. The strength of the association between disability and emotional difficulties and self-harm was greater for: maternal report of adolescent emotional difficulties; disabled adolescents with moderate/severe activity limitations; and adolescents with psychosocial impairments. Conclusions: There is a clear need for providers of all mental health services to ensure that reasonable accommodations are made to services to ensure that they are responsive to the specific needs of adolescents with disabilities. Further research is needed to determine the extent to which our results can be generalised to adolescents in other settings, to specific subgroups of adolescents with disabilities, to other measures of emotional difficulties and to other informants. Future research is also needed to further explore the consistency and determinants of the intersection between gender by disability regarding adolescent mental health.