Abstract Introduction Individuals in treatment for opioid use disorder (OUD) have high smoking rates and limited success with Food and Drug Administration (FDA)-approved cessation aids, suggesting need for novel approaches. Electronic cigarettes (e-cigarettes) might benefit this population, but e-cigarettes’ acceptability for tobacco reduction or cessation among smokers in OUD treatment is not known. Methods A cross-sectional mixed-methods study of 222 adults in OUD treatment with buprenorphine in the Boston, Massachusetts metropolitan area was conducted in 2020. We used quantitative and qualitative data to investigate individuals’ experience with and interest in e-cigarettes and other methods for smoking cessation and assessed factors associated with interest in e-cigarette use. Results One hundred sixty (72%) of the 222 participants were past 30-day cigarette smokers. They most frequently reported having ever used nicotine replacement therapy (NRT; 83%) and e-cigarettes (71%) for smoking cessation and most often indicated interest in using NRT (71%) and e-cigarettes (44%) for future smoking cessation. In multiple logistic regression analysis, interest in using e-cigarettes for future smoking cessation was independently associated with having ever used e-cigarettes for smoking cessation, current e-cigarette use, and perceiving e-cigarettes to be less harmful than cigarettes (ps < .05). In qualitative data, many current vapers/former smokers reported that e-cigarettes had been helpful for quitting cigarettes. For current smokers who currently or formerly vaped, frequently reported challenges in switching to e-cigarettes were concerns about replacing one addiction with another and e-cigarettes not adequately substituting for cigarettes. Conclusions E-cigarettes had a moderate level of acceptability for smoking cessation among cigarette smokers in OUD treatment. More research is warranted to test the efficacy of this approach. Implications Individuals in treatment for opioid use disorder (OUD) have high smoking rates and limited success with existing smoking cessation tools, suggesting a need for novel cessation treatment approaches. In this mixed-methods study of individuals receiving medication treatment for OUD with buprenorphine in Massachusetts in 2020, we found a moderate level of acceptability of e-cigarettes for smoking cessation.