Abstract Background Self-injurious behaviours, such as head banging, hair pulling, skin picking and scratching, are common in individuals with autism. Despite high prevalence rates, there is a paucity of longitudinal research to refine models of risk and mechanism and inform service planning. In this longitudinal study, we investigated self-injury in a cohort of individuals with autism over 10 years to identify behavioural and demographic characteristics associated with persistent self-injury. Methods Carers of 67 individuals with autism completed questionnaires relating to the presence of self-injury and relevant risk markers at T₁ (mean [SD] age in years 13.4 [7.7]) and T₃ (mean [SD] age in years 23.9 [7.7]) 10 years later. Forty-six of these also took part at T₂ (3 years after initial participation). Analysis assessed demographic and behavioural risk markers for self-injury, as well as the predictive value of items assessed at T₁and T_2. Results Self-injury was persistent in 44% of individuals over the 10-year period, with behavioural characteristics of impulsivity (p < .001) and overactivity (p = .002), identified as risk markers for persistence. A predictive model of self-injury was derived from LASSO analysis, with baseline impulsivity, interest and pleasure, stereotyped behaviour, social communication and adaptive functioning predicting self-injury over 10 years. Conclusions In this unique longitudinal investigation into the persistence of self-injury in a non-clinical sample of individuals with autism over a 10 year period, we have identified a novel, robust and stable profile of behavioural characteristics associated with persistent self-injury. Findings support an early intervention strategy targeted towards individuals identified to be at a higher risk of developing self-injurious behaviour.