The purpose of this study was to determine direct and indirect costs of patients with trisomy (T) 13, 18, and 21 in Thailand. Direct medical costs were obtained from Siriraj Informatics and Data Innovation Center (SiData+), Faculty of Medicine, Siriraj Hospital, and indirect costs were estimated using a human capital approach. About 241 patients with T21 had outpatient care visits and 124 patients received inpatient care. For T13 and T18, five and seven patients were analyzed for outpatient and inpatient cares, respectively. For patients with T13, T18, and T21 receiving outpatient care, total annual mean direct medical costs ranged from 183.2 USD to 655.2 USD. For inpatient care, average yearly direct medical costs varied between 2,507 USD to 14,790 USD. The mean and median increased with age. In outpatient care, costs associated with drugs and medical devices were a major factor for both T13 and T21 patients, whereas laboratory costs were substantial for T18 patients. For inpatient care, costs of drug and medical devices were the greatest for T13 patients, while service fee and operation costs were the highest for T18 and T21 patients, respectively. For outpatient care, adult patients with congenital heart disease (CHD) had significantly higher mean annual direct medical costs than those without CHD. However, all adult and pediatric patients with CHD receiving inpatient care had significantly higher costs. Patients with T13, T18, and T21 had relative lifetime costs of 22,715 USD, 11,924 USD, and 1,022,830 USD, respectively.