Background: Levels of stress and burnout increase during nursing education. This development has consequences for nursing students' health, learning, competence, and interest in quality issues in health care. Design: In a randomized controlled pilot trial with a sample of 113 nursing students the effect of an intervention using techniques from acceptance and commitment training (ACT) to prevent the development of stress and burnout was evaluated. Method: The 6 × 2-hour program was compared to standard treatment (reflection seminars) post-intervention and at a three-month follow-up using longitudinal analysis of mean response profiles. Mechanisms of change were investigated using a baseline-post intervention two-mediator model. Results: The intervention resulted in increased mindful awareness and decreased experiential avoidance, as well as decreased perceived stress and burnout. Levels of mindful awareness and perceived stress were sustained at follow-up. The proposed mechanisms of change were partly supported by the data. Conclusion: This study shows that techniques from ACT might have the potential to contribute to preventing the development of stress and burnout during nursing education. However, additional studies are needed to validate these results.