This paper describes the willingness of 1267 men who have sex with men (MSM) enrolled in a prospective HIV vaccine preparedness study from Chicago, Denver, and San Francisco to enroll in HIV vaccine efficacy trials. Respondents were interviewed at baseline and followed-up at 6, 12, and 18 months. At each visit respondents were tested for HIV antibodies using enzyme-linked immunosorbent assay (ELISA) testing with Western blot confirmation. Over 18 months, the annualized HIV seroincidence of this cohort was 2.4%. At baseline, 37% of the men reported that they would be "definitely" willing to participate in an HIV vaccine efficacy trial; however, this dropped to 21% at 12 months and remained stable at 18 months. Greater willingness to participate (WTP) was related to lower education, engaging in HIV risk behavior, living in Denver, white ethnicity, and older age. Changing WTP suggests that the decision to participate in HIV vaccine efficacy trials may be complex and dynamic and take an extended time. These data underscore the importance of informed consent and raise questions regarding the influence of decision-making processes on HIV vaccine efficacy trial design, compliance, and validity.