Background: Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour. Methods: We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched for age, gender, level of intellectual disability and mobility. Descriptive analyses were used to determine the extent to which environmental events were associated with self-injury. Results: Lag sequential analysis of the association between self-injurious behaviour and environmental events revealed no differences between the two groups in terms of either the number or degree of environmental associations. Conclusions: The results suggest that the associations between the environment and self-injury in CdLS do not differ from those seen in the broader population of people with intellectual disability. By implication the social reinforcement hypothesis is equally applicable to both groups.