Background: Individuals with autism spectrum disorder (ASD) are at particularly high risk of suicide and suicide attempts. Presentation to a hospital with self-harm is one of the strongest risk factors for later suicide. We describe the use of a novel data linkage between routinely collected education data and child and adolescent mental health data to examine whether adolescents with ASD are at higher risk than the general population of presenting to emergency care with self-harm. Methods: A retrospective cohort study was conducted on the population aged 11–17 resident in four South London boroughs between January 2009 and March 2013, attending state secondary schools, identified in the National Pupil Database (NPD). Exposure data on ASD status were derived from the NPD. We used Cox regression to model time to first self-harm presentation to the Emergency Department (ED). Results: One thousand twenty adolescents presented to the ED with self-harm, and 763 matched to the NPD. The sample for analysis included 113,286 adolescents (2.2% with ASD). For boys only, there was an increased risk of self-harm associated with ASD (adjusted hazard ratio 2·79, 95% CI 1·40–5·57, P<0·01). Several other factors including school absence, exclusion from school and having been in foster care were also associated with a higher risk of self-harm. Conclusions: This study provides evidence that ASD in boys, and other educational, social and clinical factors, are risk factors for emergency presentation with self-harm in adolescents. These findings are an important step in developing early recognition and prevention programmes.