Background: Self-injury is reported to be common in autism spectrum disorder (ASD). However, there are limited robust data detailing the prevalence, persistence, associated person characteristics and operant function of self-injury in ASD. Method: Three large scale survey studies were employed to establish the prevalence, persistence and risk markers for self-injury in ASD compared to contrast groups. Experimental functional analyses were conducted, including a fine grained temporal analysis of behaviours associated with self-injury. Results: Self-injury was displayed by 50% of the ASD sample and was persistent over three years in 77.8% of the group. Self-injury was associated with higher levels of autistic behaviour in individuals without idiopathic autism. Self-injury was associated with higher levels of impulsivity, hyperactivity, painful health conditions, repetitive behaviours and lower levels of adaptive behaviour. ‘ASD weighted’ operant functions for self-injury were identified for the majority of children with ASD. Conclusions: Self-injury is prevalent and persistent in ASD. The presence of ASD phenomenology is a risk marker for self-injury. There is a role for repetitive behaviours, pain and impaired behavioural inhibition in the development and persistence of self-injury. Self-injury is likely to be maintained by operant reinforcement in many individuals with ASD, through ‘ASD weighted’ reinforcement contingencies.