Aim To explore the clinical effect of endometrial injury (EI) on the third day of the menstrual cycle before frozen–thawed embryo transfer (frozen–thawed ET) on patients experienced two or more implantation failures. Methods A total of 200 patients who suffered at least two failed hormone‐replacement therapies and frozen–thawed ET were randomly divided into two groups: EI group and control group (n = 100 in each group). Patients in the EI group received local EI with a Pipelle catheter on the third day of the menstrual cycle before frozen–thawed ET. Primary outcomes were live birth, clinical pregnancy and implantation rates. Secondary outcomes were biochemical, multiple and ectopic pregnancy rates and abortion rates. Results The rate of live birth in EI group (51.00%) was significantly higher than that of control group (36.00%) (P = 0.032). Clinical pregnancy and implantation rates in EI group were significantly higher comparing to control group (64.00% vs 48.00%, P = 0.023 and 46.74% vs 30.11%, P = 0.001). The rate of multiple pregnancy in EI group (37.50%) was significantly higher than that of control group (18.75%) (P = 0.031). No significant difference in ectopic pregnancy rate and abortion rate was observed between EI group and control group. Conclusion Applying EI to patients experienced two or more implantation failures on the third day of the menstrual cycle before frozen–thawed ET can improve clinical outcomes.

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