Human herpesvirus-8 (HHV-8) is frequently detected in oropharyngeal secretions from HIV-infected men who have sex with men (MSM), and contact with saliva may be an important mode of HHV-8 transmission. A total of 196 MSM were followed over 2 years to determine the correlates of HHV-8 oropharyngeal shedding. A total of 134 (68%) of 196 participants were HHV-8 seropositive upon enrollment, and 9 (15%) of 62 participants seroconverted to HHV-8 during follow-up. HHV-8 DNA was detected in 43 (22%) of 196 participants: 39 (27%) of 134 HHV-8 seropositive, 4 (8%) of 53 HHV-8 seronegative, and 5 (56%) of 9 seroconverters to HHV-8. HHV-8 was detected in 101 (15%) of 696 total oral specimens: 84 (17%) of 481 samples from HHV-8-seropositive men, 6 (3%) of 180 samples from HHV-8-seronegative men, and 11 (31%) of 35 samples from seroconverters. Using adjusted marginal structural models, HHV-8 shedding was higher in men not receiving highly active antiretroviral therapy (odds ratio 2.4, 95% CI 1.0-6.0, P = 0.06), with CD4 counts > 200 cells/mm (odds ratio 4.8, 95% CI 1.0-22.8, P = 0.05), or with detectable oral leukocyte esterase (odds ratio 5.0, 95% CI 2.0-12.5, P < 0.01). CD4 count, antiretroviral therapy, and oral inflammation may influence HHV-8 oropharyngeal shedding.