PURPOSE: There is still a lack of robust data on the epidemiology of cardiac arrest during anesthesia. We investigated the frequency and risk factors of cardiac arrest during anesthesia over the past two decades at a tertiary care university hospital in Japan. METHODS: We retrospectively analyzed 111,851 anesthesia records of patients who underwent surgery under anesthesia between 2000 and 2019. Cardiac arrest cases were classified according to the patient's background, surgical status, main cause and initial rhythm of cardiac arrest, and the presence of the return of spontaneous circulation (ROSC). Univariate and multivariate logistic regression analyses were used to identify the risk factors of cardiac arrest and failure to achieve ROSC. RESULTS: Ninety cardiac arrest cases during anesthesia were identified. The incidence of cardiac arrest was 8.05 per 10,000 anesthetics (95% CI, 6.54-9.90). There were 6 anesthesia-related cardiac arrests and 9 anesthesia-contributory cardiac arrests. The most common cause of cardiac arrest was blood loss. American Society of Anesthesiologists physical status 4-5, emergency surgery, and cardiovascular surgery were identified as independent risk factors of cardiac arrest. American Society of Anesthesiologists physical status 4-5, blood loss-induced cardiac arrest, and non-shockable rhythm were independently associated with failure to achieve ROSC. CONCLUSION: Blood loss was the most common cause of cardiac arrest and blood loss-induced cardiac arrest was independently associated with failure to achieve ROSC. Further improvements in treatment strategies for bleeding may reduce the future incidence of cardiac arrest and death during anesthesia.