Fascioliasis (liver fluke disease) has raised significant public health concerns in the 15 regional provinces of Central Vietnam, accounting for 93% of the national incidence of the disease. No control measures to date have proven effective. Annual reports show increasing incidence of fascioliasis but they are incomplete. This cross-sectional study was conducted to identify the prevalence of fascioliasis and to describe its associated risks in three communes in Central Vietnam. 500 human blood samples were examined (ELISA); and a survey of knowledge, attitude and practice (KAP) was conducted for 600 randomly selected adults per commune. The findings suggest that overall seroprevalence was 7.75% (95% CI 6.54-9.16%). Among the infected cases, people aged from 18-59 years (85.6%) and farmers (68.0%) accounted for majority of infection. Less than half of participants in all three communes (24.6% - 46.0%) knew the causes of fascioliasis; and considerable proportions ate improperly boiled vegetables (28.2-33.8%), drank unboiled water (23.5-42.5%), and did not own a household toilet (14.2-20.5%). Relatively high prevalence and risks of fascioliasis were found in Central Vietnam, supporting the need for comprehensive intervention measures including selective treatment, health education, and multisectoral approaches to reduce the morbidity associated with fascioliasis and thus improve the health status of the people.