Compassion is an essential component of medical practice but is difficult to sustain over time. This problem is increasingly recognized in medical curricula. Mindfulness-based interventions have the potential to enhance compassion in medicine but this has not yet been tested. This study evaluated whether a brief mindfulness induction increased compassionate responding to difficult patients among medical students and assessed whether trait self-compassion moderated the impact of this experimental manipulation. A sample of 83 medical students completed baseline questionnaires including trait self-compassion prior to a laboratory session. In the laboratory, participants were gender block-randomized to mindfulness or control conditions before completing tasks assessing compassionate behaviour and decision-making in difficult patient vignettes. Finally, a covert behavioural measure allowed direct observation of responses to a request for help. The induction elicited mindfulness as intended and equivalently at both high and low levels of self-compassion. ANCOVAs showed that mindfulness predicted greater patient “liking” and “caring” but only among persons lower in self-compassion. The mindfulness intervention predicted greater helping behaviour, but primarily among those with higher self-compassion. A brief mindfulness induction showed some promise in enhancing compassionate responses and behaviour among medical students. Mindfulness training may offer a means of sustaining and enhancing compassion among some medical professionals but further research is needed.