Introduction Tobacco smoking is a major cause of preventable disease in Australia. Individuals receiving opiate agonist treatment (OAT) are a group who experience high tobacco-related morbidity and mortality rates. Despite reporting a desire to stop, relapse rates in OAT clients are high and cessation attempts supported by pharmacotherapy are less effective than in general populations. New and innovative ways of addressing smoking amongst this group are needed. Vaporised nicotine products (VNPs), or e-cigarettes, may reduce a person's exposure to toxicants and carcinogens when compared to tobacco cigarettes. High quality evidence indicates that VNPs can increase rates of smoking cessation compared to nicotine replacement therapy. Pilot results of VNPs as a smoking cessation aid in OAT clients suggests their use is feasible and acceptable but effectiveness in this group has not been explored. This protocol details the rationale and methodology for a randomised controlled trial to examine the effectiveness of VNPs for tobacco smoking cessation amongst OAT clients in New South Wales, Australia. Methods and Analysis This will be a randomised single-blinded parallel group trial comparing 12-weeks of 12mg/mL vaporised nicotine to best-practice NRT. Participants must be 18 years or older, accessing opiate treatment at a participating health site, and a current daily tobacco smoker seeking to quit or reduce their smoking. The primary outcome will be self-reported 7-day point prevalence abstinence from tobacco after 12-weeks of treatment. Secondary outcomes include biochemically verified abstinence, self-reported 30-day abstinence, number of cigarettes smoked each day, craving and withdrawal symptoms, and VNP safety. Between-group comparisons will be conducted at end of treatment, and at 12-weeks post-treatment. Discussion This study examines new ways of reducing tobacco related harm in individuals receiving OAT. Outcomes may be enhanced by leveraging participants interactions with health care provides who can facilitate the required support. Study findings have the potential to significantly impact tobacco smoking prevalence in priority populations. Ethics and Dissemination Protocol approval was granted by Hunter New England Human Research Ethics Committee (Reference 2020/ETH01866). Findings will be disseminated via academic conferences, peer-reviewed publications and social media. Registration The study was registered in the Australian New Zealand Clinical Trials Registry (Reference ACTRN12621000148875).

The authors have declared no competing interest.

This study was funded by New South Wales Health Translational Research Grants Scheme (Round 4)

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All data produced in the present study are available upon reasonable request to the authors