Background: Post-traumatic stress disorder (PTSD) is common in adults with intellectual disabilities. Often there are additional disorders such as substance use, mood and anxiety disorders. The current study focuses on the feasibility and initial efficacy of prolonged exposure (PE) for PTSD in adults with mild intellectual disabilities. The secondary effect of PE on additional mood, anxiety and substance use disorders is also examined. Methods: A single case experimental design (N = 12) with an A (baseline)-B (intervention) phase including a follow-up measurement after 3 months was conducted. Time series and single time points measurements were performed. Results: Six participants dropped-out. The results showed a significant decrease in PTSD symptoms and a significant decrease in additional symptoms (social avoidance, anxiety and stress), among participants who completed treatment. Conclusion: PE appears to be a feasible and effective treatment for PTSD in some adults with mild intellectual disabilities. Suggestions emerge from this study to make standard PE treatment more appropriate for adults with mild intellectual disabilities. Further research is needed to reduce drop-out in trauma treatment. Some suggestions for this are made in this study. Treatment of PTSD with PE did not appear to affect comorbid mood disorders. Further research is needed.