Cholangiocarcinoma (CCA) is common cancer in the northern and northeastern regions of Thailand. Abdominal ultrasound surveillance for CCA is a standard non-invasive imaging study for detecting an early stage of malignancy, which could potentially aim for curative treatment. From 2011 to 2017, Chulabhorn Hospital conducted a cohort on the “Study and treatment project for CCA” in the endemic area of Nan Province, Northern Thailand. The outcome proved that patients who received ultrasound surveillance had a better chance to detect in the resectable stage and eventually had a better survival outcome. However, there is limited data on the cost-effectiveness analysis of using ultrasound surveillance of CCA to be the important information for government reimbursement schemes. This research aimed to study the cost-effectiveness of the ultrasound surveillance program of CCA for high-risk populations in the northern region of ​​Thailand. By analyzing historical data from a societal perspective, a decision tree model was applied to evaluate the cost-effectiveness of ultrasound surveillance programs in populations with high risk for CCA. The results from the cost-effectiveness analysis showed that the population who received ultrasound surveillance for resectable CCA maintained the quality-adjusted life-year gained (QALY gained) of 0.13 years and the incremental cost-effectiveness ratio (ICER) of 58,242 THB/QALY gained as compared with the non-surveillance group. The ICER of 58,242 THB/QALY gained is considered within the threshold of the willingness to pay in Thailand, which is about 160,000 THB/QALY gained; therefore, ultrasound surveillance for resectable CCA is considered cost-effective and affordable. This analytic result may be useful to consider a policy to provide ultrasound surveillance for CCA in the population at risk for reimbursement.