Abstract Once-daily oral tenofovir/emtricitabine is highly effective as pre-exposure prophylaxis (PrEP) against HIV but is dependent on adherence, which may be challenging for men who have sex with men (MSM) and use substances. Digital pill systems (DPS) permit the direct, real-time measurement of adherence, though user perceptions of data privacy in this context are unknown. Thirty prospective DPS users – HIV-negative MSM with non-alcohol substance use – completed in-depth qualitative interviews exploring preferences around privacy, access, and sharing of DPS adherence data. Participants discussed some concerns about the impact of DPS use on personal privacy, and emphasized the need for robust data protections in the technology. Participants were interested in having on-demand access to their adherence data, and were most willing to share data with primary care providers and long-term relationship partners. Future investigations exploring bioethical frameworks around DPS use are warranted, and user preferences should inform best practices for protecting DPS data.