Abstract Introduction Application of tranexamic acid (TXA) in spine surgery is very frequent even without signs of hyperfibrinolysis, although its beneficial blood-saving effects are offset by harmful adverse events such as thromboembolic incidents. Thus, we investigated whether in relatively less invasive spinal procedures such as one-level posterior spinal fusion, omission of TXA affects the requirement for blood transfusions. Methods We conducted a retrospective propensity score-matched noninferiority study with 212 patients who underwent one-level posterior spine fusion and who were stratified according to whether they received TXA intraoperatively at our tertiary care center. The primary endpoint was the volume of transfused packed red cells. Testing for noninferiority or equivalence was performed by two one-sided testing procedure (TOST) with a priori defined noninferiority margins ($δ$ δ ). Results After propensity score matching a total of five patients (11.6%) treated with TXA were transfused compared with five patients (11.6%) who did not receive TXA. The majority of patients (51.2%) had a risk-increasing condition. The risk difference (no TXA–TXA) of intraoperative transfusion was − 4.7% (CI 90% − 13.62 to 4.32%), and omitting TXA was noninferior ($δ$ δ = $±$ ± 10%). The mean intergroup difference in transfused volume (no TXA–TXA) was − 23.26 ml intraoperatively (CI 90% − 69.34 to 22.83 ml) and − 46.51 ml overall (CI 90% − 181.12 to 88.1 ml), respectively, suggesting equivalence of TXA omission ($δ$ δ = $±$ ± 300 ml). The hemoglobin decline between both groups was also equivalent (with $δ$ δ = $±$ ± 1 g/dl) both on the first postoperative day ($Δ Δ$ Δ Δ Hb = 0.02 g/dl, CI 90% − 0.53 to 0.56 g/dl) and at discharge ($Δ Δ$ Δ Δ Hb = − 0.29 g/dl, CI 90% − 0.89 to 0.31 g/dl). Conclusion We demonstrated that requirement of transfusion is rare among one-level fusion surgery and the omission of TXA is noninferior with regard to blood transfusion in high-risk patients undergoing this procedure. Therefore, the prophylactic use of TXA cannot be recommended here, suggesting to focus on alternative blood conservation strategies, if necessary.