Cholangiocarcinoma (CCA) is highly prevalent in northeastern Thailand, where Opisthorchis viverrini (OV) infection is endemic. Recurrent infection may lead to repeated praziquantel (PZQ) treatment, chronic biliary inflammation, and long-term carcinogenic processes. However, population-based longitudinal evidence regarding the association between PZQ use and CCA remains limited. Therefore, this study aimed to estimate the association between PZQ use and CCA incidence in a population-based cohort. This retrospective cohort study used data from the Khon Kaen Cohort Study conducted between 1990 and 2001. A total of 17,941 participants aged 30–70 years were followed through linkage with the Khon Kaen Population-Based Cancer Registry until 2022. Participants were classified by baseline history of PZQ use, obtained from structured interviews. Missing values for PZQ use and OV infection were addressed using logistic regression-based imputation models. Generalized linear models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). As a secondary exploratory analysis, the CCA Risk Lifestyle Index (CRLI), constructed from four factors, namely PZQ use, OV infection, alcohol consumption, and smoking (range 0–4), was evaluated separately. Among participants, 3,769 (21.01%) reported PZQ use. CCA occurred in 156 PZQ users (4.14%) and 456 non-users (3.22%). PZQ use was associated with a modestly increased risk of CCA (adjusted RR = 1.22, 95% CI: 1.01–1.48). Higher CRLI scores were associated with increased CCA risk (RR = 1.23, 95% CI: 1.13–1.33). PZQ use was associated with higher CCA incidence in this cohort. However, the findings should be interpreted cautiously because residual confounding related to recurrent OV infection may remain. Further longitudinal studies are needed to clarify this relationship.
