Background: The present study examined pain perception in children and adolescents with ADHD and the interaction between pain perception and the administration of methylphenidate (MPH) in order to generate hypotheses for further research that will help to clarify the association between ADHD diagnosis, MPH treatment and pain perception. Methods: We included 260 children and adolescents of the ‘German Health Interview and Examination Survey for Children and Adolescents’ (KiGGS) and analyzed parent’s assessments of children’s pain distribution and pain perception, as well as the influence of MPH administration on pain perception in affected children and adolescents. Results: Pain perception was associated with ADHD and MPH administration, indicating that children and adolescents suffering from ADHD without MPH treatment were reported to have lower pain perception compared to both, healthy controls (HC) and ADHD patients medicated with MPH. Conclusion: We suggest that reduced pain perception in children and adolescents with ADHD not medicated with MPH may lead to higher risk tolerance by misjudgments of dangerous situations, expanding the importance of MPH administration in affected children and adolescents.