The hormonal protocol is used to increase reproductive efficiency in ewes. The aim of the study was to investigate the effects of 2 prostaglandin F2 alpha (2PGF2 alpha) and compared it with progesterone+ equine chorionic gonadotropin (P4eCG) in nulliparous Ghezel ewes. A total of 132 nulliparous ewes were randomly divided into three groups. The control group (n=42) did not receive any hormonal treatment. The P4eCG group (n=48) used of intravaginal sponge for a 12-day and an injection of 400IU of eCG at the time of sponge removal. The 2PGF2 alpha group (n=42) received the double injection of PGF2 alpha at a 9-day interval. For measurement of the progesterone (P4) concentration, three times (at the start of the experiment, at the time of withdrawal the vaginal sponge and the second injection of PGF(2 alpha) and on days 20 after mating), blood samples were taken from experimental groups ewes. Pregnancy detection was done on the 30-35 days of pregnancy using B-mode ultrasonography. The estrous rate was obtained 100% in all groups. The highest number of nulliparous ewes were in estrus 48 h after the end of the synchronization program (control: 85.8%, 2PGF2 alpha: 85.7%, P4eCG groups: 58.4%). No significant difference was observed in serum P4 concentration at the time 1 and 3 between the groups. The pregnancy and lambing rates were significantly higher (P<0.05) in the P4eCG (85.4% and 85.4%, respectively) and 2PGF(2 alpha) (83.3% and 83.3%, respectively) groups than in the control group (28.6% and 23.8%, respectively). The litter size and twin rates in the P4eCG treatment group (1.19 and 19.5%, respectively) were significantly higher (P<0.05) compared to the 2PGF(2 alpha) (1 and 0%, respectively) and control groups (1 and 0%, respectively). The fecundity rate was no statistically significant difference between the P4eCG (1.02 +/- 0.08) and 2PGF2 alpha (0.83 +/- 0.05) groups (P>0.05). Based on the results, it was concluded that 2PGF2 alpha injection can be employed to synchronize nulliparous estrus ewes in the late breeding season and is a suitable alternative for the P4eCG protocol.