This study aimed to evaluate the pregnancy rates, adverse reactions, and medication costs of two luteal phase support regimens: oral dydrogesterone and micronized vaginal progesterone (MVP) pessary in in vitro fertilization cycles. A randomized open-label trial with participants randomly assigned to either 400 mg MVP twice daily or 10 mg dydrogesterone three times daily. The primary endpoints were pregnancy rates, and the secondary endpoints included tolerance, miscarriage rates, and medication cost. Per-protocol principle analysis was performed. The baseline characteristics of the 162 participants were similar. Dydrogesterone had statistically similar (p>0.05) positive pregnancy test rates fifteen days post embryo transfer (35.8% vs. 32.7%), clinical pregnancy rates at the gestational age of 6 weeks (32.1% vs. 28.8%), ongoing pregnancy rates (26.4% vs. 23.1%) and miscarriage rates at 14 weeks of gestation (9.2% vs. 9.4%) and safety profile to MVP. Dydrogesterone was better tolerated as vaginal itching was significantly more prevalent in the MVP arm (p=0.008). Dydrogesterone is significantly less expensive than MVP pessary. Oral dydrogesterone and MVP pessary had similar pregnancy rates and adverse effects. Dydrogesterone appears more user-friendly and less expensive in cases of luteal-phase support in in vitro fertilization cycles.