Mindfulness-based relapse prevention (MBRP) is a therapy for addictive behaviors that incorporates cognitive-behavioral relapse prevention (RP) skills with mindfulness training to increase awareness and skillful action in high-risk situations. Stress is a common reason reported for substance use relapse, and using physiological measures to measure stress engagement may help us identify mechanisms of clinical improvement. Specifically, salutatory changes in HF-HRV post-treatment may serve as a marker of treatment efficacy. We investigated tonic and phasic heart rate variability (HRV) to a cognitive stressor (i.e., arithmetic challenge) following 8 weeks of RP, MBRP, or post-detox treatment known as treatment as usual (TAU; n = 34). MBRP was related to higher levels of tonic and phasic HF-HRV, lower levels of anxiety, and lower heart rate reactivity (than TAU only) compared to RP and TAU. This suggests that those who completed MBRP are engaging with stress, but perhaps in a more adaptive, flexible manner. MBRP is associated with higher cardiac vagal control and lower stress/anxious reactivity. Given that negative emotions are an important component of relapse, these results lend further support to say that mindfulness may be helpful for those with substance use disorders.