Introduction: Special concerns often arise when medical students are themselves the subjects of education research. A recently completed large, multi-center randomized controlled trial of computer-assisted learning modules for surgical clerks provided the opportunity to explore the perceived level of risk of studies where medical students serve as human subjects by reporting on: 1) the response of Institutional Review Boards (IRBs) at seven institutions to the same study protocol; and 2) the thoughts and feelings of students across study sites about being research subjects. Methods: From July 2009 to August 2010, all third-year medical students at seven collaborating institutions were eligible to participate. Patterns of IRB review of the same protocol were compared. Participation burden was calculated in terms of the time spent interacting with the modules. Focus groups were conducted with medical students at each site. Transcripts were coded by three independent reviewers and analyzed using Atlas.ti. Results: The IRBs at the seven participating institutions granted full (n=1), expedited (n=4), or exempt (n=2) review of the WISE Trial protocol. 995 (73% of those eligible) consented to participate, and 207 (20%) of these students completed all outcome measures. The average time to complete the computer modules and associated measures was 175 min. Common themes in focus groups with participant students included the desire to contribute to medical education research, the absence of coercion to consent, and the low-risk nature of the research. Discussion: Our findings demonstrate that risk assessment and the extent of review utilized for medical education research vary among IRBs. Despite variability in the perception of risk implied by differing IRB requirements, students themselves felt education research was low risk and did not consider themselves to be vulnerable. The vast majority of eligible medical students were willing to participate as research subjects. Participants acknowledged the time demands of their participation and were readily able to withdraw when those burdens became unsustainable