Objective: This research aimed to analyze the cost-effectiveness of ultrasound surveillance for Cholangiocarcinoma (CCA) in a high-risk population residing in the northern region of Thailand and compare these results with the non-surveillance patients who presented with CCA. Methods: This was a retrospective descriptive study of two groups monitored and treated for CCA in the same institute, but differing as to whether ultrasound was included in the surveillance. The ultrasound surveillance group comprised those who participated in the cohort study of CCA at Chulabhorn Hospital from 2011 to 2017. Whereas, the non-ultrasound surveillance group consisted of patients treated for CCA at Chulabhorn Hospital from 2009 to 2015 (and not part of the first group). Historical data and societal perspectives were analyzed and interpreted using a decision tree model. The results of one-way sensitivity analyses of probability and cost parameters affecting the change in incremental cost-effectiveness ratio (ICER) were analyzed and presented using tornado diagrams. Result: The ultrasound surveillance group had the quality-adjusted life years gained (QALY gained) of 0.117 years, resulting in the incremental cost-effectiveness ratio (ICER) of 152,985 Thai Baht (THB) or equal to 4,222.6 US-dollars (USD) /QALY gained which is about when compared to the non-ultrasound surveillance group. Moreover, the ICER value was within the willingness to pay (WTP) calculated for Thailand of 4,416.2 USD (160,000 THB) /QALY gained.  The probability of non-diagnostic CCA in non-ultrasound surveillance group and the cost of abdominal ultrasound were found to be major factors affecting the ICER. Conclusion: Ultrasound surveillance of CCA was cost-effective in Thailand. This information can be helpful for national policy planning in regard to Thai populations at high risk of CCA. Further study is recommended to assess cost-effectiveness in other areas with lower incidences of CCA.