Both spiritual experiences and mindfulness as a psychological variable have been identified as components of wellbeing and health. As there is uncertainty about their relationship, we have investigated the impact of spiritual experiences and mindfulness as well as their interaction on distress in chronically ill patients. The unidimensional Daily Spiritual Experiences Scale, the multidimensional Exceptional Experiences Questionnaire, the Freiburg Mindfulness Inventory, and the Brief Symptom Inventory were administered to 109 chronically ill patients. Fifty-eight patients reported regular and frequent spiritual or (...) contemplative practice from different traditions over an average of 14.7 years. Patients with regular spiritual practice reported more positive spiritual experiences, were more mindful and less distressed. A stepwise linear regression analysis revealed that the EEQ subscale “negative spiritual experiences” was the most important single predictor for psychological distress. In contrast, both the EEQ subscale “positive spiritual experiences” as well as the DSES that also captures positives daily encounters with a transcendental realm or entity did not account for a significant amount of variance in distress. Further analysis of the regression model, confirmed that NSE was still the largest predictor for distress and that mindfulness and the interaction between mindfulness and NSE were the most important buffers protecting individuals from distress. Thus, mindfulness seems not only to be a clinically important protective factor for buffering generic distress, but particularly for distress derived from NSEs. This suggests that in addition to directly facilitating well-being and health by means of positive spiritual experiences, at least some form of regular spiritual or meditative techniques seem to endow an individual with a certain degree of resilience against negative spiritual experiences that is likely a consequence of increased mindfulness. If these findings are vindicated by further studies, spiritual experiences should not be conceived and measured as univariate but rather multivariate constructs. (shrink)