Background: Although evidence-based psychological treatments for chronic pain (CP) have been demonstrated to be effective for a variety of outcomes, modest effects observed in recent reviews indicate scope for improvement. Self-compassion promotes a proactive attitude towards self-care and actively seeking relief from suffering. Consequently, more compassionate people experience better physical, psychological and interpersonal well-being. Methods: We conducted a single-blind, randomized, controlled trial to examine the effects of a Mindful Self-Compassion program (MSC) on relevant clinical outcomes in patients with CP. Patients were randomly assigned to one of the two intervention arms: MSC or cognitive-behavioural therapy (CBT). The protocols of both intervention arms were standardized and consisted of a 150-min session once a week during 8 weeks formatted to groups of no more than 20 participants. The primary outcome was self-compassion, measured with the Self-Compassion Scale (SCS). The secondary outcomes were other pain-related scores, quality-of-life measures, and anxiety and depression scores. Results: In all, 62 and 61 patients were assigned to the MSC and CBT groups, respectively. The MSC intervention was more effective than CBT for self-compassion (average treatment effect [ATE] = 0.126, p < 0.05). The secondary outcomes, pain acceptance (ATE = 5.214, p < 0.01), pain interference (ATE = −0.393, p < 0.05), catastrophizing (ATE = −2.139, p < 0.10) and anxiety (ATE = −0.902, p < 0.05), were also favoured in the experimental arm (MSC). No serious adverse events were observed. Conclusions: Mindful Self-Compassion is an appropriate therapeutic approach for CP patients and may result in greater benefits on self-compassion and emotional well-being than CBT. Significance: This randomized controlled trial compares the novel intervention (MSC program) with the gold standard psychological intervention for CP (CBT). MSC improves the levels of self-compassion, a therapeutic target that is receiving attention since the last two decades, and it also improves anxiety symptoms, pain interference and pain acceptance more than what CBT does. These results provide empirical support to guide clinical work towards the promotion of self-compassion in psychotherapeutic interventions for people with CP. How to cite this article: Torrijos-Zarcero M, Mediavilla R, Rodríguez-Vega B, et al. Mindful Self-Compassion program for chronic pain patients: A randomized controlled trial.