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The effectiveness of Mindfulness-Based Relapse Prevention (MBRP) in a naturalistic outpatient setting for those in recovery from opioid use disorder receiving medication-assisted treatment is unknown. The purpose of this pilot study was to test the effectiveness of MBRP in a naturalistic outpatient setting for those in recovery from opioid use disorder. Participants were recruited from a comprehensive opioid addiction treatment program who were in the intermediate stage of medication-assisted treatment (MAT) (at least 90 consecutive days substance free). Participants who completed the MBRP intervention served as their own controls [i.e., each participant participated in 8 weeks of treatment-as-usual (TAU) with MAT before the 8-week MBRP was initiated]. Pre/post-data analysis with study completers and non-completers (i.e., participants who did not complete the mindfulness intervention, but remained in TAU) was performed. Thirty-two participants were recruited (mean age, 36; range 21–47). No significant differences in baseline demographics were detected between the completers and non-completers. Analyses suggest significant reductions (p < 0.05) were observed in reported depression in completers compared to non-completers, and significant increases were observed in reported mindfulness (p < 0.05) in completers among those completed the MBRP intervention study phase. Trends in the hypothesized direction were also observed for anxiety (p = 0.17), but not for craving (p = 0.43). Although significant attrition was experienced, results suggest MBRP can be incorporated into a MAT in an outpatient setting, and significant positive findings were observed despite the small sample size. An unexpected finding was that patients in MAT still reported clinically significant levels of anxiety and depression that were not reduced in TAU.