Background and Purpose: Among different routes of estrogen formulations, the transdermal route has obtained popularity in recent years for endometrial preparation in HRT FET cycles .However, no clear evidence is available regarding safety and efficacy of the transdermal route. This meta-analysis investigated the safety and efficacy of oral (tablets) vs transdermal (gel/patches) estrogen formulations. Methods: A comprehensive literature search was performed for all published articles before May 30, 2022, in electronic databases, including PubMed, Cochrane Library, Embase, CINAHL, Trip Database, Worldwide Science and Google Scholar. Outcomes, including endometrial thickness, implantation rate (IR), miscarriage rate (MR), clinical pregnancy rate (CPR), and live birth rate (LBR), were measured using pooled Odds/Risk ratios (OR/RR) or standardized mean difference (SMD) with 95 % confidence intervals (CIs). Results: Eight studies involving a total of 1,198 IVF patients were included in the meta-analysis. In a pooled analysis, a trend for a higher risk of miscarriage was observed in the transdermal group compared to the oral estrogen group (RR=1.18; 95% CI= 0.84 to 1.67). However, no significant association for IR (OR=0.93; 95% CI= 0.67 to 1.29), CPR (OR=0.97; 95% CI= 0.80 to 1.19), LBR (OR=0.77; 95% CI= 0.46 to 1.29) was found between the oral vs. the transdermal estrogen groups. Conclusions: In HRT-FET cycles using oral or transdermal estrogen, no significant difference was seen regarding endometrial thickness, IR, CPR, and LBR rates; however, a trend for a higher MR was noted in the transdermal group.