BACKGROUND: Disease burden can be represented by health-related parameters such as disability-adjusted life years and economic burden. Economic burden is an important index, as it estimates the maximum possible cost reduction if a disease is prevented. This study aimed to determine the economic burden of 238 diseases and 22 injuries in Korea in 2015. METHODS: Economic burden was estimated with a human resources approach from a social perspective, and direct and indirect costs were calculated from insurance claims data and a cause of death database. Direct costs were divided into medical costs (including hospital admission, outpatient visit, and medication use) and nonmedical costs (including transportation and caregiver costs). Indirect costs from lost productivity, either from the use of healthcare service or premature death, were analyzed. RESULTS: In 2015, the estimated economic burden was USD 133.7 billion (direct: USD 65.5 billion, indirect: USD 68.2 billion). The total cost of communicable diseases was USD 16.0 billion (11.9%); non-communicable diseases, USD 92.3 billion (69.1%); and injuries, USD 25.4 billion (19.0%). Self-harm had the highest costs (USD 8.3 billion), followed by low back pain (LBP, USD 6.6 billion). For men, self-harm had the highest cost (USD 7.1 billion), while LBP was the leading cost (USD 3.7 billion) for women. CONCLUSION A high percentage of Korea's total socioeconomic disease burden is due to chronic diseases; however, unnoticed conditions such as infectious diseases, injuries, and LBP are high in certain age groups and differ by gender, emphasizing the need for targeted social interventions to manage and prevent disease risk factors.