Objective: Cognitive flexibility or attentional set-shifting capacity has long been considered a core area of executive dysfunction for individuals with autism. Whether these difficulties are due to higher-level attentional difficulties associated with comorbid ADHD remains unclear. Method: The current study compared the performance of 48 participants with autism, ADHD, autism-ADHD, and a comparison group (N = 12 per group) on a set-shifting task, which included a local–global paradigm. Results: Results of this study revealed that participants with attentional difficulties (autism + ADHD and ADHD alone) exhibited a significant shifting cost (difference between maintaining and shifting attention). Conclusion: Attentional difficulties associated with ADHD may be associated with an enhanced attentional shifting cost. Implications of these results were discussed in relation to screening for ADHD symptoms in studies of individuals with autism which seek to determine the neuropsychological profile of this condition.