Introduction While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand. Methods Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed. Results 525 participants completed the informed consent survey (Heng County, China=255, Xinjiang, China=229, Chiang Mai, Thailand=41). Mean age was (...) 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6–10 yrs vs 0–5 yrs: OR=0.27, p=0.03; more than 11 yrs vs 0–5 yrs: OR=0.18, p=0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR=0.07; p=<0.01), not minding (OR=0.26; p=0.03), being bored (OR=0.25; p=0.01) and not finding the questions easy (OR=0.10; p=<0.01). Conclusions Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent. Trial Registration clinicaltrials.gov number NCT00270257. (shrink)