INTRODUCTION: The demand for total joint arthroplasty (TJA) is increasing worldwide with excellent long-term results. In general, TJA provides several benefits to the patients but also causes possible complications. The aim of our study was to describe trends in mortality after TJA in a high-volume arthroplasty center, and to examine the potential risk factors. METHODS: From 1996 to 2018, a total of 103,560 patients (73,130 primary cases, 30,430 revision cases) underwent a TJA procedure in our institution. Anthropometric parameters, Charlson Comorbidity Index (CCI), pre- and postoperative hemoglobin (Hb), blood loss during surgery, postoperative complication (such as infection, deep vein thrombosis, pulmonary embolism, etc.) and cause of death from all patients who deceased during hospitalization were collected. The short-term mortality rate was analyzed between the primary and the revision groups. RESULTS: The short-term mortality rate within our investigated groups was low with 0.041% in primary THA, 0.299% in revision THA, 0.045% in primary TKA, 0.205% in revision TKA, 0.214% in TSA/RSA, 0.15 % in primary TAA and 0% after TEA. Significant differences were found for preoperative Hb-values in patients undergoing septic revision (10.7 g/dl) compared to patients undergoing aseptic revision (12.8 g/dl) or primary arthroplasty (13.6 g/dl) (p < 0.001). Furthermore, we found significant differences regarding CCI between the groups. The comparison between causes of death (COD) showed a significantly higher number for pulmonary embolisms in the aseptic groups, while septic shock was the leading COD in the septic group and myocardial infarction as COD was found significantly more often after primary TJA. CONCLUSION: This is the largest single-center study presenting the short-term mortality rate following TJA. Consequently, TJA is a safe procedure with a low short-term mortality rate. However, depending on the type of surgery, certain risk factors cannot be eliminated. In order to further reduce the mortality, procedures as such should continue to be performed at specialized centers under standardized conditions.