Background.In contrast to the wealth of data on human papillomavirus (HPV) infections in women, much less is known about HPV in men. Methods.Between June 2003 and March 2006, a total of 240 heterosexually active male university students 18–20 years of age were recruited for participation in a cohort study of HPV infection. Genital cell samples were collected, at 4-month intervals, for HPV-DNA analysis by polymerase chain reaction. The subjects maintained a Web-based journal of sexual activity. Results.At 24 months, the cumulative incidence of new infection of any genital HPV type was 62.4% (95% confidence interval CI, 52.6%–72.2%). Acquisition rates did not differ by genital site (i.e., glans, penile shaft, or scrotum) of initial detection (P = .86). The most commonly detected types were HPV-84 and HPV-16. In multivariate analysis, a report of a new sex partner during the prior 0–4 (hazards ratio HR, 2.0 95% CI, 1.3–3.0) and 5–8 (HR, 1.8 95% CI, 1.2–2.7) months and a history of smoking (HR, 1.6 95% CI, 1.1–2.4) were associated with an elevated risk of HPV acquisition. Conclusion.Genital HPV infection is common and multifocal in young men, and its incidence is higher than that reported for similar cohorts of young women. The high rates of HPV infection in men should be considered when strategies for the prevention of HPV infection in female adolescents and young women are being developed.