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ABSTRACT: In dairy cattle production, it is important to understand how inbreeding affects production, fertility, and health traits. However, there is still limited use of genomic information to estimate inbreeding, despite advancements in genotyping technologies. To address this gap, we investigated the effect of inbreeding on German Holstein dairy cattle using both pedigree-based and genomic-based inbreeding estimators. We employed one method based on pedigree information (Fped) together with 6 genomic-based methods, including 3 genome-wide complex trait analysis software estimators (Fhat1, Fhat2, Fhat3), VanRaden's first method (FVR1, with observed allele frequencies, and FVR0.5, when allele frequencies are set to 0.5), and one based on runs of homozygosity (Froh). Data from 24,489 cows with both phenotypes and genotypes were used, with a pedigree including 232,780 animals born between 1970 and 2018. We analyzed the effects of inbreeding depression on production, fertility, and health traits separately, using single-trait linear animal models as well as threshold models to account for the binary nature of the health traits. For the health traits, we transformed solutions from the liability scale to a probability scale for easier interpretation. Our results showed that the mean inbreeding coefficients from all estimators ranged from −0.003 to 0.243, with negative values observed for most genomic-based methods. We found out that a 1% increase in inbreeding caused a depression ranging from 25.94 kg (Fhat1) to 40.62 kg (Fhat3), 1.18 kg (Fhat2) to 1.70 kg (Fhat3), 0.90 kg (Fhat2) to 1.45 kg (Froh and Fhat3), 0.19 (Fped) to 0.34 d (Fhat3) for 305-d milk yield, fat, protein, and calving interval, respectively. The health traits showed very slight gradual changes when inbreeding was increased steadily from 0% to 50%, with digital dermatitis showing a rather contrasting trend to that of mastitis, which increased the more an animal was inbred. Overall, our study highlights the importance of considering both pedigree-based and genomic-based inbreeding estimators when assessing the impact on inbreeding, emphasizing that not all inbreeding is harmful.