Objective: To determine the influence of geographic, knowledge and behavioral factors on Opisthorchis (O.) viverrini infection in the Northeast of Thailand. Methods: This cross-sectional study was conducted by using four datasets of years 2016 and 2017. Generalized linear mixed model was employed to analyze association between geographic, knowledge and behavioral factors and O. viverrini infection. Results: Totally there were 1 885 participants. The prevalence of O. viverrini infection was 10.03%. Geographic factors that showed statistically significant association with O. viverrini infection in the Northeast region were featured by at least a dam and reservoir (Adj. OR = 4.21, 95%CI: 2.49-7.13, P < 0.001), at least a weir (Adj. OR = 1.74, 95%CI: 1.09-2.77, P = 0.020), > 50 dogs and cats per village (Adj. OR = 3.40, 95%CI: 2.17-5.31, P < 0.001), and rice fields covered > 50% of its areas (Adj. OR = 1.91, 95%CI: 1.04-4.01, P = 0.036), as well as low to moderate levels of knowledge (Adj. OR = 1.60, 95%CI: 1.32 to 1.94, P < 0.001), consumed raw fish (Adj. OR = 1.90, 95%CI: 1.02 to 3.52, P = 0.040) and consumed processed raw fish (Adj. OR = 3.03, 95%CI: 2.20 to 4.18, P < 0.001). Other significant covariates were gender and age of the respondents. Conclusions: O. viverrini infection still remains a public health problem of the Northeast of Thailand. Geographic and demographic factors, knowledge, and consumption behaviors of raw fish products are significantly associated with O. viverrini infection.