Objectives Chronic pain affects 1 in 5 Europeans, with a prevalence in Spain of 11%. It is one of the main causes of medical consultation and is associated with high personal, social, and economic costs with diverse psychological repercussions. Several studies have shown the effectiveness of psychological therapies in the treatment of chronic pain, including mindfulness-based therapies. In this regard, mindfulness-based pain management (MBPM) has evidenced significant positive changes in patients with chronic pain, but so far, no RCT study has been conducted. Therefore, the main purpose of this study is to explore the results of the MBPM program with chronic pain patients. Additionally, we will analyze the differential efficacy of the MBPM program on fibromyalgia versus non-fibromyalgia chronic pain patients. Methods Ninety patients with chronic pain were randomized to experimental group MBPM (50 patients) and wait-list control group (40 patients) and assessed at pre- and post-treatment in demographic and pain-related variables, psychopathological symptoms, cognitive variables, resilience, and quality of life. Results Findings showed moderate to large effects in favor of the experimental group in pain management and acceptance, use of analgesics, psychopathological symptoms, general negative thoughts, self-blame, mental-health-related quality of life, and resilience. Non-fibromyalgia chronic pain patients benefited significantly more than participants with fibromyalgia. Conclusions The positive impact of the MBPM program on critical variables related to chronic pain provides evidence of its efficacy, which could be enhanced with the inclusion of complementary therapeutic CBT components to address sleep problems, need for control, and rumination. Trial Registration ClinicalTrials.gov (NCT03992612).