〔Abstract〕 Objective To investigate the application effect of natural cycle endometrial preparation and artificial cycle endometrial preparation after descending modulation in the cycle of vitrification frozen embryo transfer (FET). Methods A total of 74 patients who underwent vitrification FET treatment and first received single blastocyst (high-quality blastocyst with a mass of more than 3BB) transplantation at the Assisted Reproduction Center of Xuzhou Maternal and Child Health Hospital from January 2021 to December 2021 were selected and divided into a NC group and a G-HRT group, 37 cases each, according to their different endometrial preparation plans. All patients in the NC group underwent natural cycle endometrial preparation, and all patients in the G-HRT group underwent artificial cycle endometrial preparation after descending modulation. Both groups underwent single blastocyst transplantation, and the clinical outcomes of the two groups were compared. Results The endometrial thickness of the G-HRT group was (10.22 ± 0.44) mm, compared with that of the NC group (10.18 ± 0.38) mm, there was no significant difference (P > 0.05). The rate of type A endometrium in the G-HRT group was 59.46% (22/37), compared with 59.46% (22/37) in the NC group, there was no significant difference (P > 0.05). There was no significant difference in the rate of early abortion and ectopic pregnancy between the two groups (P > 0.05). The clinical pregnancy rate of the G-HRT group was significantly higher than that of the NC group, and the difference was statistically significant (P < 0.05). Conclusion Compared with the natural cycle, in the vitrification FET cycle, the endometrial preparation using artificial cycle after descending modulation can improve the endometrial receptivity and increase the clinical pregnancy rate, which is an effective endometrial preparation scheme for vitrification FET.