Background: This study aimed to understand the clinical and economic burden associated with postsurgical complications in high-risk surgeries in Thailand. Methods: A cost and outcome study was conducted using a retrospective cohort database from 4 tertiary hospitals. All patients with high-risk surgeries visiting the hospitals from 2011 to 2017 were included. Outcomes included major postsurgical complications, length of stay (LOS), in-hospital death, and total healthcare costs. Multivariate regression analyses were performed to identify risk factors of postsurgical outcomes. Results: A total of 14,930 patients were identified with an average age of 57.7 ± 17.0 years and 34.9% being male. Gastrointestinal procedures were the most common high-risk procedures, accounting for 54.9% of the patients, followed by cardiovascular procedures (25.2%). Approximately 27.2% of the patients experienced major postsurgical complications. The top 3 complications were respiratory failure (14.0%), renal failure (3.5%), and myocardial infarction (3.4%). In-hospital death was 10.0%. The median LOS was 9 days. The median total costs of all included patients were 2,592 US$(IQR: 1,399 to 6,168 US$). The patients, who received high-risk gastrointestinal surgeries and experienced major complications, had significantly increased risk of in-hospital death (OR: 4.53; 95%CI: 3.81-5.38), longer LOS (6.53 days; 95%CI: 2.60-10.46 days) and higher median total costs (2,465 US$; 95%CI: 1,945-2,984 US$), compared to those without major complications. Besides, the patients, who underwent high-risk cardiovascular surgeries and developed major complications, resulted in significantly elevated risk of in-hospital death (OR: 2.22; 95%CI: 1.74-2.84) and increased median total costs (2,719 US$; 95%CI: 2,129-3,310 US$), compared to those without major complications. Conclusions: Postsurgical complications are a serious problem in Thailand, as they are associated with worsening mortality risk, LOS, and healthcare costs. Clinicians should develop interventions to prevent or effectively treat postsurgical complications to mitigate such burdens.