@#Opisthorchis viverrini infection is still one of the public health problems in Southeast Asia. In Thailand alone, more than three million people are estimated to be currently infected. Opisthorchiasis may cause severe biliary diseases, eventually leading to fatal cholangiocarcinoma. This study aimed to investigate the prevalence and risk factors of opisthorchiasis in two rural communities along the Nam Kam River in the northeastern region of Thailand. A cross-sectional study was conducted in Phon Na Kaeo District of Sakon Nakhon Province and That Phanom District of Nakhon Phanom Province in Thailand between March and June 2017. Faecal samples were collected and examined for the presence of O. viverrini by Kato-Katz technique. Socio-demographic variables and risk factors were collected by a standardised questionnaire. The overall prevalence of O. viverrini among 495 study participants was 15.4% (95% confidence interval [CI] 12.3 – 18.8). The parasite rate was higher in Nakhon Phanom than in Sakon Nakhon (P = 0.009) and differed significantly in adults <45 years old in both provinces (P <0.05). Multivariate regression analyses revealed being labourer (adjusted odd ratio [AOR] 4.7 [95% CI 1.08, 20.38], P = 0.039) and farmer (AOR 5.79 [95% CI 1.45, 31.91], P = 0.015) were positively associated with a higher risk of O. viverrini infection. This study highlights O. viverrini infection as a significant endemic disease with potential health problems among the water-based communities along the Nam Kam River. For country with high O. viverrini transmission, such information will be useful for designing efficient strategic interventions.