The aim of the present study was to compare the efficacy and satisfaction rate of combined therapy of oral micronized progesterone capsules and vaginal progesterone gel versus monotherapy with vaginal progesterone gel in luteal support. A case-control study was performed on a total number of 370 women aged <45 years undergoing IVF-ET treatment. The patients received either combination of Crinone 8% vaginal gel, 90 mg daily dose and Utrogestan oral capsules 3 x 100 mg, or Crinone 8% vaginal gel, 90 mg daily. Progesterone supplementation begun on the day of oocyte retrieval and continued until pregnancy was tested and in the case of pregnancy until week 8. The comparable rates of ongoing pregnancies were noted with use of combined-progesterone therapy (39.5%) and progesterone-monotherapy (33.5%). Abortion rate (6.4% vs. 15.6%) was significantly lower with the use of combined therapy. Tolerability and satisfaction of both supplements was almost equal but bleeding occurred more frequently in the progesterone-monotherapy group. In conclusion, the efficacy, satisfaction and tolerability of combined and vaginal progesterone supplements were comparable, but bleeding in early pregnancy and abortion rate presented more frequently with the use of vaginal progesterone.