Background: In HIV prevention trials, there is ethical concern that some participants have a “preventive misconception,” an overestimate of the probability or level of personal protection afforded by participating in the trial. The purpose of this study was to collect preliminary quantitative data using a brief measure of preventive misconception (PREMIS) in an HIV prevention trial. Methods: PREMIS was administered at the week 4 and 40 visits to participants in HPTN 069/ACTG 5305 [NCT01505114], a multicenter trial in the United States that included 4 arms comparing investigational maraviroc-containing regimens (vs. tenofovir/emtricitabine) for preexposure prophylaxis in men and women who have sex with men who were at risk of HIV infection. Descriptive statistics were computed for all responses. Paired t tests were used to assess item responses between weeks 4 and 40. Results: Responses to PREMIS items did not differ significantly between weeks 4 and 40 (n=429), so only the latter are summarized. When asked about their confidence that the study medications would prevent them from acquiring HIV, 20% did not know or were unsure; the remaining respondents expressed high confidence (median, 80%; IQR, 60%-90%). When asked which study group they thought they were in, 66.2% said they did not know. Most (62.7%) believed they were assigned randomly to their group, whereas 9.8% believed a doctor chose the best group for them. When asked how many participants out of 100 would have their chance of acquiring HIV reduced, respondents gave similar responses for all 4 study groups (all medians = 80; 30.4%-37.6% answered “don''t know/unsure”). Responses among respondents who thought they knew which group they were in were similar regarding the chance of benefit for the group in which they believed they were in (median, 80 out of 100 participants; 21.2% “don''t know/unsure”). Conclusions: These data suggest that most trial participants expressed high confidence in a prevention effect due to their belief that all of the study groups had a high likelihood of benefit. Future work should assess the relationship of responses to PREMIS, reported risk behaviors, and HIV seroconversion to place these data into context.