Abstract: Objective This study aimed to explore the hemostatic effect of tranexamic acid in patients undergoing double-segment posterior lumbar interbody fusion (PLIF). Methods 105 cases of dual-segment PLIF patients admitted to Shandong Province Wendeng Osteopathic Hospital from April 2020 to November 2023 were included as the study subjects. They were randomly divided into two groups using a random number table method: an observation group (n =53, given tranexamic acid, TXA) and a control group (n =52, given the same volume of 0.9% sodium chloride solution). Perioperative blood loss, coagulation parameters were compared between the two groups. Results Compared with the control group, the TXA group exhibited significantly lower intraoperative visible blood loss, hidden blood loss, postoperative drainage volume, and total blood loss, as well as earlier drainage tube removal (one-sided P ＜ 0.025). At 24 h and 72 h postoperatively, hemoglobin (Hb) and hematocrit (HCT) levels in both groups were significantly lower than preoperative levels (one-sided P ＜ 0.025), but the TXA group maintained higher Hb and HCT levels than the control group (one-sided P ＜ 0.025). At 24 h and 72 h postoperatively, prothrombin time (PT) and activated partial thromboplastin time (APTT) were shortened, while fibrinogen (FIB) and D-dimer (D-D) levels were elevated compared with preoperative values in both groups (one-sided P ＜ 0.025). However, no significant differences were observed between the two groups in APTT, PT, FIB, or D-D levels (two-sided P ＞ 0.05). Both groups showed reduced visual analog scale (VAS) scores at drainage tube removal and discharge compared with preoperative scores (one-sided P ＜ 0.025), but the TXA group had lower VAS scores at tube removal than the control group (one-sided P ＜ 0.025). No thrombotic complications, occurred in either group during hospitalization. Conclusion The administration of tranexamic acid in patients undergoing two-level PLIF effectively reduces perioperative blood loss with significant hemostatic efficacy and a high safety profile.