OBJECTIVES: Approximately 10% (40 000) of US quitline enrollees who smoke cigarettes report current use of electronic nicotine delivery systems (ENDS); however, little is known about callers' ENDS use. Our aim was to describe why and how quitline callers use ENDS, their beliefs about ENDS and the impact of ENDS use on callers' quit processes and use of FDA-approved cessation medications. DESIGN: Qualitative interviews conducted 1-month postregistration. Interviews were recorded, transcribed, double-coded and analysed to identify themes. SETTING: Oklahoma Tobacco Helpline. PARTICIPANTS: 40 callers aged ≥18 who were seeking help to quit smoking were using ENDS at registration and completed ≥1 programme calls. RESULTS: At 1-month postregistration interview, 80% of callers had smoked cigarettes in the last 7 days, almost two-thirds were using ENDS, and half were using cessation medications. Nearly all believed ENDS helped them quit or cut down on smoking; however, participants were split on whether they would recommend cessation medications, ENDS or both together for quitting. Confusion and misinformation about potential harms of ENDS and cessation medications were reported. Participants reported using ENDS in potentially adaptive ways (eg, using ENDS to cut down and nicotine replacement therapy to quit, and stepping down nicotine in ENDS to wean off ENDS after quitting) and maladaptive ways (eg, frequent automatic ENDS use, using ENDS in situations they did not previously smoke, cutting down on smoking using ENDS without a schedule or plan to quit), which could impact the likelihood of quitting smoking or continuing ENDS use. CONCLUSIONS: These qualitative findings suggest quitline callers who use ENDS experience confusion and misinformation about ENDS and FDA-approved cessation medications. Callers also use ENDS in ways that may not facilitate quitting smoking. Opportunities exist for quitlines to educate ENDS users and help them create a coordinated plan most likely to result in completely quitting combustible tobacco.