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Introduction: HIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years). However, those findings may not reflect population-wide HIV rates in FFC since the study population was selected for high-risk behaviour. Methods: Between September 2011 and March 2013, we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At baseline (September 2011-January 2012), a household enumeration census was done in eight fishing communities (one lakeshore and seven islands), after which a random sample of 2200 participants aged 18-49 years was selected from 5360 individuals. Interviewer-administered questionnaire data were collected on HIV risk behaviours and WTP, and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation. Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were determined using log-binomial regression models. Results: Overall baseline HIV prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%, p B0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%), farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was higher among women than men (adj.PPR = 1.50, 95%; 1.20, 1.87) and participants aged 30-39 years (adj.PPR = 1.40, 95%; 1.10,1.79) and 40-49 years (adj.PPR = 1.41, 95%; 1.04,1.92) compared to those aged 18-24 years. Other factors associated with HIV prevalence included low education, previous marriage, polygamous marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p= 0.004) and among island communities compared to lakeshore ones (90.4% vs. 85.8%, p= 0.004). Conclusions: The HIV prevalence in the general fisher-folk population in Uganda is similar to that observed in the 'high-risk' fisher folk. FFC have very high levels of willingness to participate in future HIV vaccine trials. Keywords: HIV-1; willingness to participate in HIV vaccine trials; fishing communities; Uganda., Introduction Globally, the HIV pandemic is most severe in East and Southern African countries, where the regional epidemics are generalized and stable or declining [1]. In generalized HIV epidemics, transmission [...]