Introduction: Femoral shaft fractures (FSFs) are associated with significant blood loss, resulting in anemia and hemorrhagic shock. However, there has been limited data for the blood loss of FSFs during the whole perioperative period. Our primary aim is to quantify the blood loss associated with FSFs treated with intramedullary nail or locking compression plate fixation, as well as to identify the relative affecting factors for perioperative hidden blood loss (HBL). Patients and methods: 131 consecutive patients with FSFs were enrolled in the retrospective study between January 2009 and January 2020, including 90 cases for intramedullary nail (Nail group) and 41 cases for locking compression plate fixation (Plate group). Demographics and perioperative data were collected and analyzed. Total blood loss (TBL), visible blood loss (VBL), HBL, and percentage of HBL (PHBL) were calculated based on hematocrit (Hct) changes. Results: There was a large drop of hemoglobin (Hb) during the perioperative time. Of all 131 patients, the average HBL was 1445.5 +/- 443.2 mL, accounting for 78.7% of TBL (1815.1 +/- 446.3 mL). TBL and HBL in Nail group were 1886.1 +/- 438.6 mL and 1546.0 +/- 424.7 mL; while TBL and HBL in Plate group were 1659.5 +/- 427.9 mL and 1225.1 +/- 405.7 mL. The differences between the two groups were statistically significant (p = 0.007, p < 0.001, respectively). Besides, statistical significance (p< 0.05, p< 0.05, respectively) was also reported in HBL between Type-A and Type-C, and between Type-B and Type-C (1395.8 +/- 44 4.8 mL vs. 1651.6 +/- 495.7 mL; and 1411.2 +/- 383.4 mL vs. 1651.6 +/- 495.7 mL, respectively). Conclusions: Patients of FSFs had significant TBL and HBL, the amount of which was much larger than that observed intra-operatively. Moreover, two readily available preoperative factors for nail fixation and Type-C were associated with a higher likelihood of more HBL. Therefore, it was argued that regular perioperative monitoring and timely blood transfusion were crucially important for patients to avoid possible risks of anemia and facilitate recovery. (C) 2021 Elsevier Ltd. All rights reserved.