Epilepsy surgery is proven as a cost-effective treatment in developed countries, especially in adults with drug resistant epilepsy (DRE). This study is aimed to demonstrate the cost-effectiveness of epilepsy surgery in children and adolescents with DRE at three years compared with those who were eligible for surgery but received medical treatment. This study was conducted from January 2014 to December 2018. Clinical data were obtained from a retrospective chart review. Direct medical costs, including epilepsy surgery, inpatient and outpatient treatment were retrieved from the finance department. Direct non-medical costs were collected from the family interview. The effectiveness was determined by percent seizure reduction and quality of life assessed by EQ-5D scores. Decision tree analysis using TreeAge Pro® 2018 was deployed to determine the cost-effectiveness. Seventeen patients had epilepsy surgery and 19 were in the medical group. Seizure freedom was noted in 52% and 16% in the surgical and medical groups, respectively. Incremental cost-effectiveness ratio (ICER) was 743,040 THB (22,793 USD) per 1 QALY and 3302 THB (101 USD) per 1% seizure reduction. The study did not demonstrate cost-effectiveness of epilepsy surgery in the short term compared with Thailand’s threshold (160,000 THB (4908 USD) per 1 QALY). Epilepsy surgery may be cost-effective if evaluated beyond three years.