Objective: To compare the clinical efficacy of two long-acting gonadotropin-releasing hormone agonists (GnRH-a) in down-regulation combined with hormone replacement cycle frozen-thawed embryo transfer (FET). Methods: A retrospective cohort study of 462 frozen-thawed blastocyst transfer cycles using two different long-acting GnRH-a for endometrial preparation was performed at the Department of Reproductive Medicine, Women’s Hospital of Nanjing Medical University from November 1, 2019 to January 31, 2021, including 324 cycles in the triptorelin group and 138 cycles in the leuprorelin group. Logistic regression model was used to analyze the relationship between two long-acting GnRH-a and the clinical efficacy of frozen-thawed blastocyst transfer. Results: The level of LH [(2.70±1.28) mUI/ mL] on estrogen initiation day was higher than that in triptorelin group [(2.41±1.19) mUI/ mL], P=0.017]; The implantation rate of leuprorelin group(62.6%) was higher than that of triptorelin group (54.6%), and the difference was statistically significant(P=0.044);the clinical pregnancy rate was increased compared with the triptorelin group, but the difference was not statistically significant (P=0.334), and the early abortion rate was decreased compared with the triptorelin group, but the difference was not statistically significant (P=0.490). In the logistic regression model, after adjusting for confounding factors including age, number of blastocyst, number of good-quality blastocyst, the level of LH on estrogen initiation day and endometrium thickness, the adjusted OR value of clinical pregnancy rate in leuprorelin group versus triptorelin group was 1.493(95% CI= 0.932~2.392), P=0.095. Conclusion: In the down-regulation combined with hormone replacement cycle of frozen-thawed blastocyst transplantation, both leuprorelin and triptorelin can achieve satisfactory down-regulation effect, leuprorelin can improve the blastocyst implantation rate, and obtain similar clinical outcomes with triptorelin.