This study aimed to determine and describe HIV-negative gay men's willingness to participate in HIV vaccine trials. Data were from participants who completed face-to-face interviews during the first 18 months (to the end of 2002) of recruitment into the Health in Men cohort of HIV-negative gay men in Sydney. A key outcome measure was a scale of Willingness to Participate in HIV Vaccine Trials, with scores ranging from 1 (unwilling) to 4 (willing). The 903 participants ranged in age from 18 to 75 years (median = 36). Mean of Willingness to Participate in HIV Vaccine Trials was 2.53 (standard deviation = 0.54), with approximately 51% of the men having a score greater than the midpoint of 2.50. A reduced linear regression model yielded four significant independent associations with Willingness to Participate in HIV Vaccine Trials: lack of tertiary education (P < 0.001),having engaged 'in the previous six months' in any unprotected anal intercourse with casual or non-concordant regular partners (P < 0.001), higher self-rated likelihood of HIV infection (P < 0.01), and higher mean scores on a scale of Comfort with Participation in HIV Vaccine Trials (P < 0.001). The willingness of HIV-negative gay men at potentially higher risk for HIV to participate in HIV vaccine trials augurs well for enrolment in HIV vaccine efficacy trials. Recruitment into trials is likely to be enhanced by addressing salient concerns such as confidentiality and vaccine-induced antibody positivity. Also, it will be important to ensure that gay men are educated and fully informed about HIV vaccines and trial processes.