Background: Positive behaviour support (PBS) emphasises multi-component interventions by natural intervention agents to help people overcome challenging behaviours. This paper investigates which components are most effective and which factors might mediate effectiveness. Method: Sixty-one staff working with individuals with intellectual disability and challenging behaviours completed longitudinal competency-based training in PBS. Each staff participant conducted a functional assessment and developed and implemented a PBS plan for one prioritised individual. A total of 1,272 interventions were available for analysis. Measures of challenging behaviour were taken at baseline, after 6 months, and at an average of 26 months follow-up. Results: There was a significant reduction in the frequency, management difficulty, and episodic severity of challenging behaviour over the duration of the study. Escape was identified by staff as the most common function, accounting for 77% of challenging behaviours. The most commonly implemented components of intervention were setting event changes and quality-of-life-based interventions. Conclusion: Only treatment acceptability was found to be related to decreases in behavioural frequency. No single intervention component was found to have a greater association with reductions in challenging behaviour. (Contains 4 figures and 6 tables.)