OBJECTIVE To determine whether luteal support of dydrogesterone may enhance the outcome of frozen-thawed embryo transfer (FET) in natural cycles by comparing the FET outcomes of different luteal support methods. METHODS A total of 2 248 natural FET cycles with an endometrial thickness of 8-12 mm and type A on ovulation day, from January 2011 to March 2013 were chosen. Oral dydrogesterone (n = 1 967) or intramuscular progesterone (n = 281) was used for luteal support. The rates of clinical pregnancy, implantation, ectopic pregnancy, miscarriage and live birth were compared among these groups. RESULTS The patients receiving oral dydrogesterone or intramuscular progesterone had similar profiles of age, type of infertility, endometrial thickness and average numbers of embryo transfer. The dydrogesterone group had higher rates of clinical pregnancy (43.26% vs 38.79%) and implantation (25.76% vs 21.13%). However a lower miscarriage rate (17.27% vs 22.02%) was insignificant. The rates of ectopic pregnancy, premature birth and live birth were also similar. When infertile factors were considered, the dydrogesterone group had significantly higher clinical pregnancy rates (43.78% vs 34.38%, P < 0.05), lowered miscarriage rates (16.54% vs 29.55%, P < 0.05) and increased live birth rates (34.16% vs 23.44%, P < 0.05) among simple tubal factor patients. CONCLUSIONS Oral administration of dydrogesterone for luteal support offers more advantages in natural cycle FET than intramuscular progesterone, especially for simple tubal factor infertility.