Psychophysiological disorders due to work-related stress continue to be highly costly for health systems and approaches for cost-effective and easily accessible interventions are much needed. Both heart rate variability-biofeedback (HRV-Bfb) and mindfulness-based interventions (MBI) have been empirically shown to reduce stress. This study compares these two interventions in the work context to a wait-list-control-group (WLC). In this three-armed randomized controlled trial (RCT), 69 healthy adults employed in the same organization were randomized to participate in HRV-Bfb, MBI or the WLC. Participants were assessed for psychophysiological parameters of stress (stress perception, coping, HRV parameters and cortisol) and stress related symptoms (depressive symptoms, psychological wellbeing, mindfulness and self-compassion). Participants trained using either HRV-Bfb or MBI for 6 weeks on a daily basis. Outcomes were assessed at baseline, after the intervention and at follow-up 12 weeks later. Results did not show any statistically significant differences between HRV-Bfb and MBI groups, and neither of the intervention groups (IGs) differed from the WLC. Findings suggest an overall reduction in stress for all groups, including the WLC, with mostly small to medium effect sizes. However, it is important to note that participants with higher baseline stress levels might benefit more from mindfulness and biofeedback-based stress reduction interventions. The results have to be interpreted with caution due to the relatively small sample size. MBI might have a slightly stronger effect on stress reduction in comparison to HRV-Bfb, as suggested by the effect sizes. This study highlights issues and challenges of the implementation of such interventions in corporate health management.