Background <p>Rett syndrome is a rare neurodevelopmental disorder associated with an increased risk of severe respiratory dysfunction and cardiorespiratory instability. In some individuals, particularly those with autonomic dysfunction or QT interval prolongation, life-threatening cardiac events may occur. Given the frequency of life-threatening emergencies in affected children, it is essential that primary caregivers are trained in pediatric basic life support (PBLS). This pilot study aimed to evaluate the effectiveness of simulation-based PBLS training for caregivers of children with Rett syndrome.</p> Methods <p>Ten caregivers, all members of the Turkish Rett Syndrome Federation and primary caregivers of affected children, participated in a structured PBLS training program conducted in a university-based simulation center. Participants underwent pre- and post-training performance assessments using simulation scenarios based on the 2021 European Resuscitation Council (ERC) PBLS guidelines. Performance was scored using a standardized checklist, and post-training feedback was collected through a satisfaction questionnaire.</p> Results <p>Pre-training scores indicated limited PBLS proficiency (mean:15.9/100). Post-training performance improved significantly (mean: 79.3/100), with notable gains across all critical PBLS steps. Questionnaire results confirmed high levels of participant satisfaction, increased self-confidence, and a perceived sense of preparedness for emergency response.</p> Conclusion <p>Simulation-based PBLS training is an effective educational approach for caregivers of children with Rett syndrome, leading to substantial improvement in both skill acquisition and confidence. This initiative represents the first effort in Turkey to utilize medical simulation centers for caregiver education in the context of rare diseases, highlighting its potential for broader public health applications.</p> Trial registration <p>Clinical trial number: not applicable.</p>