Widespread discrimination across much of sub-Saharan Africa against persons with same-sex sexuality, including recent attempts in Uganda to extend criminal sanctions against same-sex behavior, are likely to have profound effects on this group's health, health care access, and well-being. Yet knowledge of the prevalence of same-sex sexuality in this region is scarce. This study aimed to systematically examine prevalence of same-sex sexuality and related health risks in young Ugandan adults. We conducted two cross-sectional survey studies in south-western Uganda targeting student samples (n = 980, n = 1954) representing 80% and 72% of the entire undergraduate classes attending a university in 2005 and 2010, respectively. A questionnaire assessed items concerning same-sex sexuality (same-sex attraction/fantasies, same-sex sexual relations), mental health, substance use, experience of violence, risky sexual behavior, and sexual health counseling needs. Our findings showed that same-sex sexual attraction/fantasies and behavior were common among male and female students, with 10-25% reporting having sexual attraction/fantasies regarding persons of the same-sex, and 6-16% reporting same-sex sexual relations. Experiences of same-sex sexuality were associated with health risks, e.g. poor mental health (2010, AOR = 1.5; 95% CI: 1.0-2.3), sexual coercion (2010, AOR 2.9; CI: 1.9-4.6), and unmet sexual health counseling needs (2010, AOR 2.2; CI: 1.4-3.3). This first study of young adults in Uganda with same-sex sexuality found high levels of health needs but poor access to health care. Effective response is likely to require major shifts in current policy, efforts to reduce stigmatization, and reorientation of health services to better meet the needs of this vulnerable group of young people.