Background: Although total knee arthroplasty (TKA) is considered an effective treatment for knee osteoarthritis, it carries risks of complications. With a growing number of TKAs performed on older patients, understanding the cause of mortality is crucial to enhance the safety of TKA. This study aimed to identify the major causes of short- and long-term mortality after TKA and report mortality trends for major causes of death. Methods: A total of 4,124 patients who underwent TKA were analyzed. The average age at surgery was 70.7 years. The average follow-up time was 73.5 months. The causes of death were retrospectively collected through Korean Statistical Information Service and classified into 13 subgroups based on the International Classification of Diseases-10 code. The short- and long-term causes of death were identified within the time-to-death intervals of 30, 60, 90, 180, 180 days, and > 180 days. Standard mortality ratios (SMRs) and cumulative incidence of deaths were computed to examine mortality trends after TKA. Results: The short-term mortality rate was 0.07% for 30 days, 0.1% for 60 days, 0.2% for 90 days, and 0.2% for 180 days. Malignant neoplasm and cardiovascular disease were the main short-term causes of death. The long-term (> 180 days) mortality rate was 6.2%. Malignant neoplasm (35%), others (11.7%), and respiratory disease (10.1%) were the major long-term causes of death.Men had a higher cumulative risk of death for respiratory, metabolic, and cardiovascular diseases. Age-adjusted mortality was significantly higher in TKA patients aged 70 years (SMR, 4.3; 95% confidence interval [CI], 3.3–5.4) and between 70 and 79 years (SMR 2.9; 95% CI, 2.5–3.5) than that in the general population. Conclusions The short-term mortality rate after TKA was low, and most of the causes were unrelated to TKA. The major causes of long-term death were consistent with previous findings. Our findings can be used as counseling data to understand the survival and mortality of TKA patients.