OBJECTIVE: The opioid crisis in the USA remains severe during the COVID-19 pandemic, which has reduced access to evidence-based interventions. This Stage 1 randomized controlled trial (RCT) assessed the preliminary efficacy of Zoom-based Mindfulness-Oriented Recovery Enhancement (MORE) plus Just-in-Time Adaptive Intervention (JITAI) prompts to practice mindfulness triggered by wearable sensors (MORE + JITAI). METHOD: Opioid-treated chronic pain patients (n = 63) were randomized to MORE + JITAI or a Zoom-based supportive group (SG) psychotherapy control. Participants completed ecological momentary assessments (EMA) of craving and pain (co-primary outcomes), as well as positive affect, and stress at one random probe per day for 90 days. EMA probes were also triggered when a wearable sensor detected the presence of physiological stress, as indicated by changes in heart rate variability (HRV), at which time participants in MORE + JITAI were prompted by an app to engage in audio-guided mindfulness practice. RESULTS: EMA showed significantly greater reductions in craving, pain, and stress, and increased positive affect over time for participants in MORE + JITAI than for participants in SG. JITAI-initiated mindfulness practice was associated with significant improvements in these variables, as well as increases in HRV. Machine learning predicted JITAI-initiated mindfulness practice effectiveness with reasonable sensitivity and specificity. CONCLUSIONS: In this pilot trial, MORE + JITAI demonstrated preliminary efficacy for reducing opioid craving and pain, two factors implicated in opioid misuse. MORE + JITAI is a promising intervention that warrants investigation in a fully powered RCT. PREREGISTRATION: This study is registered on ClinicalTrials.gov (NCT04567043).