Opisthorchis viverrini is an ongoing public health problem in Northeast Thailand. Despite continuous efforts for decades by healthcare organizations to overcome this problem, infection rates remain high. To enable related personnel to identify and address the various issues effectively, a cross-sectional study was performed to investigate prevalence and risk factors for opisthorchiasis. The target group was 3,916 Thai residents of Northeast Thailand who were 15 or over. Participants were recruited using the 30 clusters sampling technique. The data were gathered through questionnaires, focus group discussions, in-depth interviews, and stool examinations for parasite eggs (using the Modified Kato Katz method). The data were analyzed using descriptive and inference statistics; in order to ascertain the risk factors and test them using the odds ratio and multiple logistic regressions. The prevalence of opisthorchiasis was 22.7% (95%CI: 0.26 to 0.24). The province with the highest prevalence was Nakhorn Phanom (40.9%; female to male ratio =1:1.2). The age group with the highest prevalence was 40-49 year olds. All age groups had a prevalence >20%. Four of seven provinces had a prevalence >20%. The factors related to opisthorchiasis were (a) sex, (b) age (especially > 50), (c) proximity and duration living near a water body, and (d) eating raw and/or fermented fish. In order to reduce the prevalence of opisthorchiasis, the focus in populations living in upper Northeast Thailand should be changing their eating behaviors as appropriate to their tradition and context.