Objectives This study aimed to explore the effectiveness of mindfulness-based relapse prevention (MBRP) with individuals receiving medication for opioid use disorder (MOUD) in a naturalistic, open-ended outpatient group treatment setting. Methods Eighty participants (mean age 36.3) who had at least 90 consecutive days substance free self-selected into treatment (MBRP, n = 35) or comparison groups (treatment as usual, TAU, n = 45). Outcomes tracked included treatment retention and relapse, and self-reported craving, anxiety, depression, and mindfulness at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. MBRP group participants attended biweekly 60-min sessions for 24 weeks. A linear mixed model analysis of variance determined the significance of the MBRP intervention on changes in craving, anxiety, depression, and mindfulness. Results No significant differences in sex, education level, insurance status, relationship status, or employment status were detected at baseline between groups. The 36-week retention (74%, MBRP/MOUD; 71%, TAU/MOUD) and relapse rates (43%, MBRP/MOUD; 47%, TAU/MOUD) were similar for the groups. There were only four relapses on opioids. Significant reductions ( p < .05) were observed in the MBRP/MOUD group for craving, anxiety, and depression in addition to significant increases in mindfulness compared to those in TAU/MOUD. Conclusions Although state and federal resources are available to expand MOUD, no standard of behavioral therapy has been established as most complimentary to MOUD. The current study results suggest MBRP can be implemented as an outpatient therapy for individuals in MOUD.