Consistent over-reporting of product use limits researchers’ ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting.