Purpose: The aim of study was to assesse the effectiveness and safety of combined treatment with TXA and EPO during the surgery for intertrochanteric fractures(IFs). Methods: Patients with IFs underwent closed reduction and internal fixation proximal femoral nail antirotation (PFNA) from January 2018 and January 2022 were enrolled in this study. The patients were randomly divided into 3 groups: control group (Group A), TXA alone group (Group B), TXA combined with EPO group (Group C). TXA dissolved in 100 mL of saline was administered intravenously at a dose of 15mg/kg over 10 minutes before and after surgery. EPO was injected subcutaneously every other day with 10000U/L. Whereas only 100 mL of saline solution was used in Group A. Perioperative total blood loss, obvious blood loss, and hidden blood loss in the there groups were calculated separately. The blood transfusion rate and volume, haemoglobin levels, postoperative drainage, operative time, and hospitalization day were recorded. Surgery-related complications including thromboembolic events, pulmonary embolism, wound hematoma and infection, cardiovascular and cerebrovascular accidents, respiratory infections, and patient mortality were also recorded to assess the safety. Results: A total of 174 patients, including 62 patients in Group A, 57 in Group B, and 55 in Group C, were enrolled in the study. Mean follow-up was at least 12.2 months for three groups. The patients in the three groups showed similar outcomes regarding the number of cases, age, gender, BMI. EPO and iron significantly improved perioperative anemia in patients with IFs(Group C, p<0.05).There was a trend toward decreased transfusion rate and volume in the TXA group (Group B and Group C, p<0.05). The Group C had advantages over the other two groups in early postoperative functional recovery, hidden blood loss, postoperative drainage, postoperative hospitalization time without increasing the risk of thrombosis and other complications(P<0.05). There were no serious complications occurring during our study. In all cases, fractures healed well and no revision surgery was performed for internal fixation failure during the follow-up. Conclusions: Combined treatment with TXA and EPO significantly improved preoperative anemia and reduced perioperative blood loss rate and volume without increasing the rate of complications in elderly patients with IFs underwent surgery of PFNA.