Recent years have been marked by an increase in electronic cigarette (e-cigarette) use. Although some evidence suggests that e-cigarettes used in isolation may be less harmful than combustible cigarettes, e-cigarette use carries significant health risks. Data are critically needed to identify risk factors that promote and maintain e-cigarette use. The current project examined how the relation between pain interference (i.e., how much pain interferes with daily functioning) and cognitive processes of e-cigarette use (i.e., perceived barriers for quitting e-cigarettes, perceived risks of e-cigarettes, and negative expectancies of using e-cigarettes) differ across sex. Participants included 340 (61.5% female; 77.1% Caucasian/White; Mage = 36.68 years, SD = 10.75) adult past-month e-cigarette users. Results suggested that increased pain interference was more strongly related to greater perceived barriers to cessation, perceived risks of e-cigarettes, and negative expectancies of using e-cigarettes among males relative to females. Importantly, this work suggests that e-cigarette use may operate differently than other substances that have been studied in the past in that male e-cigarette users may be more vulnerable than female e-cigarette users to the effects of pain interference on cognitive processes of e-cigarette use. (PsycInfo Database Record (c) 2022 APA, all rights reserved).