Sexual and nonsexual modes of transmission of human herpesvirus 8 (HHV8) have been suggested, but specific routes remian unclear. Therefore, the objective of this study was to assess risk factors for HHV8 seropositivty and determine specific sexual practice associated with HHV8 seroconversion. Sera from 1, 458 homosexual men (Amsterdam Cohort Study, 1984–1996) were tested for antibodies to HHV8 with a modified version of an enzyme immunoassay, using recombinant HHV8 lytic phase capsid (ORF65) and latent phase nuclear (ORF73) proteins. HHV8 seroprevalence at study entry was 20.9% (305/1, 458); was highest among those with positive human immunodeficiency virus (HIV) status, no steady partner, and southern European or Latin American nationality; and increased with older age and higher number of sexual partners. During followup, 215 men seroconverted for HHV8 (incidence: 3.6/100 person-years). Both prevalence and incidence rates remained more or less table during the study period. Orogenital insertive sex (odds ration (OR) = 5.95; 95% confidence interval (CI): 2.88, 12.29) or orogential receptive sex (OR = 4.29; 95% CI: 2.11, 8.71) with more than five partners in the past 6 months, older age (OR = 2.89; 95% CI: 1.13, 7.34, when oldern than 45 years), and preceding HIV infection (OR = 2.47; 95% CI: 1.53, 3.99) were independent predictors for HHVB seroconversion. The authors found strong evidence for orogenital transmission of HHV8 among homosexual men. Am J Epidemiol 2000; 151: 21324.