The present study aimed to compare the reproductive outcomes after the blind application of the standard Ovsynch and Presynch Ovsynch protocols on Egyptian Buffaloes (Bubalus bubalis) during the breeding season. Fifty multiparous Egyptian buffalo cows of an unknown stage of the estrous cycle were randomly divided into two groups: 1) the standard Ovsynch protocol (first GnRH (G1) at d0, PGF 2α at d7 , and second GnRH; G2 56 h later and 2) the pre-synch Ovsynch (G6G-Ovsynch) protocol (PGF 2α and GnRH 2 days apart 6 days before starting G1 of the standard Ovsynch). Cows were subjected to timed artificial insemination (TAI) 16 and 40 h after the G2 injection in both groups. Blood sampling and ovarian transrectal ultrasonography were performed at three time points, PGF2α, G2, and 2 days after G2. Serum progesterone (P 4 ) (ng/mL) concentrations were significantly higher in the G6G-Ovsynch group than in the Ovsynch group at the time of PGF 2α and two days after the G2 injection, but they were lower (P ˂ 0.05) at the G2 injection. The Vascularity index of the corpus luteum (CL) and dominant follicle (DF) wall area (%) were higher (P ˂ 0.05) in the G6G-Ovsynch group compared to the Ovsynch group. The ovulatory response indicated by the presence of CL at d7 was significantly higher in G6G-Ovsynch than in Ovsynch (73 vs. 51%, respectively). Moreover, a higher (P ˂ 0.05) pregnancy rate was observed in G6G-Ovsynch than in the Ovsynch group. In conclusion, the blind application of the G6G-Ovsynch improved the ovulatory response in the early stages of the synchronization protocol and raised the pregnancy rates in Egyptian buffaloes. .