BACKGROUND: So far, studies investigating Mindfulness Based Stress Reduction (MBSR) training in medical students are conducted in self-selected, pre-clinical samples, with modest response rates without collecting data on non-participants. This study first examines interest and participation rates of students starting their clinical clerkships. Second, it compares students interested in a mindfulness training with non-interested students and students participating in a trial on the effect of MBSR with non-participating students on levels of psychological distress, personality traits, cognitive styles and mindfulness skills. METHODS: We examined two student samples from the Radboud University Medical Center, Nijmegen: Study 1 From March to December 2010 we performed a cross-sectional pilot-study among 4th year medical students starting their clinical clerkships, assessing interest in a MBSR training. We compared scores on the Brief Symptom Inventory, the Neo Five Factor Inventory and the Five Facet Mindfulness Questionnaire of interested students with those of non-interested students using t-tests with Bonferroni correction. Study 2 From February 2011 to August 2012 we invited 4th year medical students starting their clinical clerkships to participate in a randomized controlled trial (RCT) on the effectiveness of MBSR. We compared scores on the Brief Symptom Inventory, the Irrational Beliefs Inventory and the Five Facet Mindfulness Questionnaire of participating students with those of non-participants using t-tests with Bonferroni correction. RESULTS: Study 1: Ninety-five out of 179 participating students (53%) were interested in a MBSR training. Interested students scored significantly higher on psychological distress (p = .004) and neuroticism (p < .001), than 84 non-interested students. Study 2: Of 232 eligible students, 167 (72%) participated in our RCT. Participants scored significantly higher on psychological distress (p = .001), worrying (p = .002), problem avoidance (p = .005) and lower on mindfulness skills (p = .002) than 41 non-participants. CONCLUSIONS: Interest in mindfulness training and response rates in a RCT on the effectiveness of MBSR among clinical clerkship students are equal to (study 1) or higher (study 2) than in studies on pre-clinical students. Interested students and participants in a RCT reported more psychological distress and psychopathology related character traits. Participants scored lower on mindfulness skills.