To evaluate the efficacy of GnRH agonists (GnRH-a) as sole luteal phase support in patients undergoing IVF in antagonist-based cycles compared with standard vaginal P preparations. Retrospective cohort. Private fertility clinic. Patients who underwent antagonist-based cycles performed at our clinic between 2009 and 2015. Intranasal GnRH-a or vaginal P as luteal support. Live birth rates. A total of 2,529 antagonist-based cycles from 1,479 women were available for analysis, in which GnRH-a were used in 1,436 cycles (56.7%) and P supplementation in 1,093 cycles (43.2%). Significantly higher live birth rates were demonstrated for the entire GnRH-a group compared with the P group. This result was even more prominent when women older than 35 years were considered separately. Furthermore, after adjustment for age, body mass index (BMI), past obstetric history, number of IVF cycles, oocyte retrieved and embryos transferred, GnRH-a was still associated with a higher rate of live birth (odds ratio 1.46, 95% confidence interval 1.10-1.94). Once a positive β-hCG was achieved, chemical pregnancy rates (PRs) and miscarriage rates were not statistically different between the GnRH-a and the P supplementation group, and GnRH-a was associated with a higher rate of live births (odds ratio 1.59, 95% confidence interval 1.07-2.36). This large retrospective study suggests that repeated intranasal GnRH-a for luteal phase support is associated with a higher live birth rate compared with standard P supplementations.