Fertility programs were implemented for the first postpartum timed artificial insemination (TAI) in 800 (primiparous and multiparous) lactating dairy cows, evaluating 2 presynchronization (presynch) strategies and 2 TAI protocols, in a 2 x 2 factorial arrangement. Weekly, cows were enrolled into 1 of 4 groups (Ovs+Ovs [Double-Ovsynch], Ovs+OvsP4/E2, PreP4/E2+Ovs, and PreP4/E2+OvsP4/E2 [Double E-Synch]). On d -17 (34 +/- 3 DIM), the Ovsynch [Ovs] presynch was initiated with 10 mu g of buserelin acetate (GnRH), and cows received 0.5 mg of cloprostenol sodium PGF2 alpha analog (PGF) on d -10, and 10 mu g of GnRH on d -7. The PreP4/E2 presynch was initiated on d -17 with a used 2-g progesterone (P4) insert, which was removed on d -10, together with 0.5 mg of PGF and 1 mg of estradiol (E2) cypionate (EC). For TAI protocols, Ovs group received the following: on d 0, 20 mu g of GnRH (double dose); on d 7, PGF; on d 8, PGF; on d 9.5, 10 mu g of GnRH; and on d 10, TAI (16 h after GnRH). Cows submitted to OvsP4/E2 received the following: on d 0, 20 mu g of GnRH (double dose) and a new 2-g P4 insert; on d 7, PGF; on d 8, P4 insert removal, PGF, and EC; and on d 10, TAI (48 h after P4 insert removal). The GLIMMIX procedure of SAS 9.4 was used for statistical analyses (P <= 0.05). The presence of corpus luteum (CL) on d -17 (average = 68.8% [550/800]) was similar among treatments. The presence of CL on d 0 of TAI protocols was high, and Ovs as a presynch increased percentage of cows with CL (95.5% [382/400] vs. 90.8% [363/400]). However, at the first PGF of the breeding (TAI) protocols (d 7), there was no effect of presynchronization program and 98.5% (788/800) of the cows had at least 1 CL. Ovulation after d 0 was greater in cows submitted to PreP4/E2 than Ovs (72.0% [288/400] vs. 64.3% [257/400]), and those ovulating had greater pregnancies per artificial insemination (P/AI; 51.0% [278/545] vs. 41.6% [106/255]). Overall, multiple ovulations after TAI were low and similar between TAI protocols and presynch strategies (7.2% [54/753]). Expression of estrus in OvsP4/E2 protocols was greater than Ovs (69.4% [274/395] vs. 41.5% [168/405]), and an interaction was detected, in which cows not expressing estrus ovulated more after TAI in Ovs compared with OvsP4/E2 protocol (93.3 [221/237] vs. 77.7% [94/121]). Cows expressing estrus had greater P/AI in both Ovs (58.3 [98/168] vs. 42.2% [100/237]) and OvsP4/E2 (57.3 [157/274] vs. 24.0% [29/121]). There was no interaction between presynch and TAI protocol on P/AI on d 32 of cows that ovulated after TAI (48.4%, 49.7%, 53.3%, and 52.5% for Ovs+Ovs, Ovs+OvsP4/E2, PreP4/E2+Ovs, and PreP4/E2+OvsP4/E2, respectively), and no differences in pregnancy loss between d 32 and 90 (average = 24.0% [92/384]). In conclusion, the study validated 2 presynchronization strategies and 2 TAI protocols, establishing 4 possible fertility programs, all of them producing well-controlled ovarian dynamics, excellent synchronization, and high fertility. Moreover, DoubleOvsynch and Double E-Synch both produced similar results, despite differences in pharmacological bases.