Tibetan patients undergoing total knee arthroplasty (TKA) have greater fluctuations in perioperative haemoglobin levels and blood hypercoagulability. This study was to investigate whether ethnicity and altitude affect perioperative blood loss and the risk of complications after TKA. We retrospectively enrolled 1,116 patients undergoing TKA for knee osteoarthritis at our hospital between January 2016 and September 2021. We divided patients into four groups according to whether they were of Tibetan or Han ethnicity and whether they lived above or below 2500m above sea level. Primary outcomes were total, intraoperative, and hidden blood losses, while secondary outcomes were complications and homologous transfusion. Factors associated with increased blood loss were analyzed by multivariate regression. Total blood loss was higher among patients residing at high altitude compared with lower altitude, whether they were of Han (794.6 mL vs. 667.2 mL, P = 0.020) or Tibetan (904.4 mL vs. 663.8 mL, P < 0.001). Total blood loss was similar between the two ethnic groups at the same altitude. Altitude, but not Tibetan ethnicity, remained associated with increased blood loss after being analyzed by multivariate regression. Complications among the four groups were generally similar, although the frequency of calf muscular venous thrombosis was higher among Tibetan patients, while the frequency of blood transfusion was higher among Han subjects. Our findings indicate that residence at high altitude, but not ethnicity, may contribute to increased total blood loss during TKA. Thrombotic complications were more frequent among Tibetan than Han patients.