BACKGROUND: Mindfulness-based interventions (MBIs) are effective for some, but not all patients with anxiety disorders, but no clinical features have been consistently able to differentiate which patients are more likely to respond. In this study, we tested heart rate variability (HRV), a proposed correlate of regulated emotional response, as a moderator of treatment response to an MBI compared with pharmacotherapy. METHODS: Seventy-seven patients with GAD had HRV data collected before randomization to pharmacological treatment with fluoxetine or Body-in-Mind Training (an MBI focused on bodily movement attention). HRV was used to predict treatment response measured by the Hamilton anxiety rating scale at 0 (baseline), 5, and 8 weeks (end of the intervention). RESULTS: The HF (nu) index of HRV was a strong moderator of treatment response between BMT and fluoxetine (estimate = 4.27 95%CI [1.19, 8.19]). Although fluoxetine was overall slightly superior to BMT in this study, no differences were found between groups in patients with high HF (nu) scores (estimate = -1.85 CI95% [-9.21, 5.52]). In contrast, patients with low HF (nu) achieved lower anxiety rating scores with fluoxetine treatment when compared with BMT (estimate = -10.29, 95% CI [-17.59, -2.99]). LIMITATIONS: A relatively small sample of patients was included. CONCLUSIONS: HRV was able to identify a subgroup for which MBI was less effective than pharmacotherapy and is a promising candidate as a selective biomarker for treatment response between an MBI and fluoxetine.