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This observational study was conducted to evaluate the effect of transition cow health on pregnancy per AI (P/AI) and pregnancy loss (PL) in cows synchronized with a Double-Ovsynch protocol (DO) for first service. Lactating Holstein cows (n = 15,041) from one commercial dairy farm in Northern Germany between January 2015 to December 2021 were enrolled into a modified Double-Ovsynch protocol (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 24 h later PGF2α, 32 h later GnRH, and 16 to 18 h later timed AI) for first service at 72 ± 3 DIM. Parity was classified as 1st, 2nd, and ≥3rd lactations. At d 32 and d 60 post-AI, cows underwent pregnancy diagnosis through transrectal ultrasound. Pregnancy loss was defined as the proportion of pregnant cows on 32 d post-AI that were found nonpregnant on 60 d post-AI. Health related events (i.e., milk fever, ketosis, retained fetal membranes, metritis, mastitis, displaced abomasum) were assessed by farm personnel using standard operating procedures. Multivariable logistic regression was used for testing potential associations between disease occurrence and outcome variables, including P/AI and PL. There were 20.0% (885/4,430), 34.9% (1,391/3,989), and 53.9% (3,570/6,622) of cows with at least one disease event for 1st, 2nd and ≥3rd lactations, respectively. In 1st lactation cows the most prevalent disease was metritis (10.7%; [473/4,430]). Cows in 2nd lactation suffered mostly from mastitis (16.6%; [664/3,989] and ketosis (16.6%; [661/3,989]). Cows in ≥3rd lactations were mostly affected by ketosis (33.2%; [2,198/6,622]). We observed a negative association of inflammatory disorders (i.e., retained fetal membranes, metritis, mastitis) and P/AI in all cows irrespective of parity. Metabolic disorders (i.e., hypocalcemia, ketosis and displaced abomasum) were negatively associated with P/AI only in multiparous cows. Irrespective of parity, only uterine diseases (i.e., retained fetal membranes, metritis) were significantly associated with PL. These results highlight the importance of optimizing transition cow health as a prerequisite for achieving high fertility in a DO protocol.