ABSTRACT Combustible cigarettes (CC) use among persons with opioid use disorders (OUD), including those in OUD methadone and buprenorphine treatment programs (OUDTP), is nearly universal (75~95%). Contributing to premature mortality and poor quality of life, CC may also promote relapse to opioids. CC smokers in OUDTP particularly suffer from severe intolerance to nicotine withdrawal discomfort. Even with potent, evidence-based nicotine replacement therapy (NRT) and extended care interventions, no study has found even modest rates of sustained CC abstinence among CC smokers in OUDTP. Electronic cigarettes (EC) may be superior to traditional NRT approaches for tobacco harm reduction either by successful switching to EC completely, or by substantially reducing the number of cigarettes smoked per day (CPD). The goal of this R01 application is to test the effectiveness of an 8-week telehealth counseling EC harm reduction intervention on CPD reduction among adult (≥ 21 years) CC smokers in OUDTP. We propose conducting a randomized controlled trial (RCT; N=302) to compare telehealth counseling + nicotine EC (Intervention) vs. telehealth counseling + combination NRT (Control) on CPD reduction. Our intervention approach is guided by the Information-Motivation-Behavioral Skills model. We will recruit our sample from OUDTP in New York City using electronic health records, in addition to participant and provider-initiated approaches. The primary outcome at end-of-intervention (8 weeks) is the proportion of CC smokers achieving 100% CPD reduction [i.e. switching completely to EC (Intervention Arm) or achieving CC abstinence (Control Arm)], verified by exhaled carbon monoxide. Secondary outcomes include 100% CPD reduction at 26- and 52-weeks, percent change in CPD relative to baseline, improvement in markers associated with health outcomes (respiratory symptoms, and health-related quality of life), and reduction in smoking toxicant exposure as measured by NNAL (a tobacco- specific carcinogen metabolite) in urine. The specific aims are to: 1) Compare the effect of EC versus NRT on CPD reduction outcomes, 2) Estimate and compare the effect of EC versus NRT on health outcomes and CC smoking exposure, 3) Evaluate moderating and mediating factors of the intervention effectiveness. In Year 1, we will finalize the intervention protocols, surveys, hire and train staff, and create the study database for proactive recruitment. Recruitment of participants will begin in Year 2 and will roll out over 24 months. There is a vital need for high‐quality RCTs evaluating EC as a tobacco harm reduction strategy. If effective, EC would provide an additional tool for tobacco harm reduction among CC smokers in OUDTP. This research has implications for OUD treatment, as well as tobacco use treatment policy and EC regulations.