Few analytic opportunities have allowed us to evaluate the role that specific sexual acts and male latex condoms play in the acquisition of external anal warts (EAW) using longitudinal data. The acquisition of EAWs occurs from epithelial contact with other HPV-infected surfaces, and hence is dependent upon sexual behaviour. Our objectives were to classify the relative importance of condom use, receptive anal intercourse (RAI) and prior history of EGWs on acquisition of EAWs. The observational Multicenter AIDS Cohort Study followed 2925 men over nine semiannual study visits for behavioural and physical examinations with laboratory testing. The main outcome measure was the occurrence of examiner-diagnosed EAWs in a homosexual population. EAWs were diagnosed among 10% of men studied across 22,157 visits reviewed for this study. Men with history of EGWs were more likely than those previously unaffected to have developed EAWs (cOR = 2.4 (2.0, 2.9)), as were men who reported multiple anoreceptive intercourse partners (e.g., compared with men who reported no RAI partners, men with 1, 2-5, > or = 6 RAI partners had crude risk ratios 1.0 (0.8, 1.3), 1.6 (1.2, 2.1), 3.9 (2.7, 5.8), respectively). These relations persisted after other demographic and sexual risk factors were controlled for in the analyses. Consistent condom usage showed no protective effect for EAWs in our crude or adjusted analyses. Patient education messages should be tailored to reflect our uncertainty about the protective nature of condoms for the development of anal warts, but to continue to assert the protective effects of a limited lifetime number of sexual partners and the heightened risk for wart recurrence once infected.