ObjectivesLittle is known about the perspectives of staff working in prisons where e-cigarettes are permitted. Scotland now permits people in custody (PiC), but not staff/visitors to use e-cigarettes, following implementation of smoke-free prisons policy in 2018. Previous studies, conducted before and immediately after the introduction of e-cigarettes in Scottish prisons, have evidenced stakeholder support for their use by PiC. This study focuses on key challenges associated with e-cigarette use in prisons, using data collected from prison staff once e-cigarettes had been allowed in a smoke-free environment for 6–9 months.SettingFive prisons in Scotland.ParticipantsSixteen qualitative interviews were conducted with prison staff from five prisons varying by population (sex, age and sentence length). Data were managed and analysed using the framework approach.ResultsWhile these staff confirmed strong support for the smoke-free prison policy and reported some benefits of replacing tobacco with e-cigarettes, they also spoke of the challenges e-cigarettes pose. These included: workplace e-cigarette vapour exposures; perceptions that e-cigarettes provide a new, effective way for some PiC to take illegal drugs, particularly new psychoactive substances; organisational challenges relating to the value attached to e-cigarettes in prisons; and implications for long-term nicotine use and tobacco cessation. Staff anticipated difficulties in tightening restrictions on e-cigarette use by PiC given its scale and significance among this population.ConclusionsMaximising the benefits of e-cigarette use by PiC is likely to require multiple measures to support effective and safe use and e-cigarette reduction/cessation where desired. This includes monitoring any misuse of e-cigarettes, and provision of guidance and support on appropriate e-cigarette use and how to limit or quit use if desired. Findings are relevant to jurisdictions considering or planning changes in prison smoking or vaping policies.