We evaluated the effect of an additional prostaglandin F_2α (PGF_2α) treatment at the initiation of a 7-d CO-Synch + CIDR synchronization of estrus protocol in a Split-time AI program. Our objective was to determine if estrus response and fixed-time AI (FTAI) pregnancy rate could be enhanced by regressing existing corpora lutea at the initiation of synchronization. Postpartum (> 80d), multiparous commercial Angus (Bos taurus) cows (n = 263) were synchronized in 3 experimental groups over the span of 2 yr on a large ranch in West Texas. Experiment 1: Estrus responses to synchronization were greater (P < 0.01) for animals receiving additional PGF_2α (+PG) (80.77%) at CIDR insertion than Control cows (54.17%). Conception rates of Estrual Cows (EC) had a tendency (P = 0.054) to be greater (64.18%) than non-estrual cows (NEC) (43.75%). Conception rate of EC was greater (P < 0.05) for Control (80.77%) than the +PG (53.66%). Experiment 2: Estrus responses were similar (P > 0.05) between treatment (+PG = 70.45%) and (Control = 61.54%). Conception rates were similar (P > 0.05) between EC (69.05%) and NEC (30.95%). Conception rates of EC was greater (P < 0.05) for +PG (61.29%) than the Control (31.25%) opposite of Experiment 1. Experiment 3: Estrus responses to synchronization were greater (P < 0.01) for +PG (83.78%) than Control cows (53.33%). Conception rates were greater (P < 0.05) for EC (76.60%) than NEC (45.00%). Conception rates of EC did not differ (P > 0.05) between +PG (77.42%) and Control (75.00).