To determine pharmacokinetic profiles of two times a day and three times a day dosage regimens of Endometrin, a micronized progesterone vaginal insert for luteal support in assisted reproductive technology, compared with a gel.A single-center, randomized, open-label, single-day, and multiple-day (5 days) parallel design pharmacokinetic study.University clinical research unit.Three groups of six healthy subjects, ages 18 to 40 years.Endometrin vaginal inserts two times a day or three times a day, or gel daily.Pharmacokinetic profiles.Progesterone serum concentrations increased rapidly following administration of Endometrin vaginal insert, producing higher peak concentrations (C max ) and clearing faster than gel. On the single day of dosing, mean C max was 17.0 ± 2.7 ng/mL in the two times a day group, 19.8 ± 2.9 ng/mL in the three times a day group, and 6.82 ± 1.69 ng/mL in the gel group. Endometrin treatments reached steady state within the first 2 days (24–36 hours), much more rapidly than the gel, which had not reached steady state by 5 days. At 5 days, the Endometrin treatments produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours.Endometrin vaginal inserts reached higher C max , produced greater systemic exposure (area under the curve 0–24), achieved steady state more rapidly, and cleared more rapidly after termination of therapy than the comparator.