Background: Student life can be stressful. Hence, we started a regular mind-body medical stress management program in 2006. By today, more than 500 students took part and evaluations showed significant results, especially with regard to a reduction of stress warning signals. For further analysis, we now decided to run a randomized controlled longitudinal trial. Methods: Participating students at Coburg University were randomized into an intervention (n = 24) or a waitlist control group (n = 19). The intervention group completed 3 sets (pre/post/follow-up) and the control group 2 sets (pre/post) of self-administered questionnaires. The questionnaires included: SF-12 Health Survey, Perceived Stress Scale (PSS), Sense of Coherence (SOC-L9), Visual Analogue Scale (VAS) concerning stress, and the Stress Warning Signs (SWS) scale. Randomly selected participants of the intervention group were also queried in qualitative interviews. The intervention consisted of an 8 week stress management group program (mind-body medical stress reduction - MBMSR). Follow-up measures were taken after 6 months. Results: Virtually, no drop-out occurred. Our study showed significant effects in the intervention group concerning SF-12 Mental Component Scale (p = 0.05), SF-12 Physical Component Scale (p = 0.001), VAS (in general, p = 0.001) and SWS (emotional reactions, p <0.001), underlined by qualitative results, which showed a higher quality of life. Conclusions: The effectiveness of an MBMSR program in a group of supposedly healthy students could be demonstrated. Findings suggest that stress management might be given importance at universities that care for the performance, the quality of life, and stress-health status of their students, acknowledging and accounting for the challenging circumstances of university life, as well as the specific needs of the modern student population.