Background: Many patients develop tumour recurrence within a few years after undergoing surgical resection of gastrointestinal stromal tumours (GIST). Adjuvant imatinib treatment is recommended for patients with high risk of GIST recurrence as it can improve recurrence-free survival and overall survival of patients. This study aims to assess the cost-utility of adjuvant imatinib in patients with high risk of GIST recurrence after surgery compared with no adjuvant therapy in Thailand. Methods: A Markov model was developed to estimate lifetime costs and outcomes of using adjuvant imatinib treatment and other treatment alternatives if recurrence occurred compared with the current situation of no adjuvant therapy in high-risk patients after surgery. A 1-month cycle length was deployed in the model. Transition probabilities were derived from literature review. Costs were collected and calculated for the year 2014 from a societal perspective. Future costs and outcomes were discounted at 3% per year. One-way and probabilistic sensitivity analyses were conducted to assess parameter uncertainties. Results: Three years of adjuvant imatinib treatment followed by imatinib treatment and best supportive care if recurrence occurred after or during adjuvant therapy, respectively, was the best option as it produced more health outcomes (1.23 life years (LYs) and 1.16 quality-adjusted life years (QALYs)) compared to no adjuvant therapy while yielding the lowest incremental cost-effectiveness ratio (ICER) of 1,648,801 Thai Baht (THB) per QALY gained. Three years of adjuvant imatinib treatment followed by sunitinib treatment if recurrence occurred had an ICER of 2,608,264 THB per QALY gained compared to the best option, while other options were dominated. A one-way sensitivity analysis showed that the utility of patients receiving adjuvant imatinib had the greatest effect on the model, followed by the discount rate and probability of GIST recurrence. Conclusions: Adjuvant imatinib treatment improved the health benefits of patients with high risk of GIST recurrence. However, in the Thai context, it was not cost-effective at the current price.