Insufficient data are available about the association between prepartum risk factors including dietary cation–anion difference (DCAD) status and postpartum outcomes of Holstein dairy cows within commercial management systems. The first objective of this experiment was to assess the association between postpartum serum calcium (Ca) dynamics and the risk of metritis development. The second objective was to identify the association of risk factors, including DCAD status of prepartum ration, prepartum serum macrominerals and parity, with the development of subclinical hypocalcemia (SCH) in two commercial herds. Herd A (n = 32) fed a negative DCAD close-up ration and herd B (n = 30) fed a positive DCAD close-up diet. A receiver operating characteristic (ROC) curve was run to evaluate the association of serum Ca concentration at 1, 2, and 4 DIM with the risk of developing metritis. A second ROC curve was also created to assess the association of prepartum serum Mg, P, and Ca concentration with the postpartum serum Ca concentration dichotomized into normocalcemic (>8.82 mg/dl) and subclinical hypocalcemic (≤8.82 mg/dl). A logistic regression model was created to assess prepartum DCAD status (negative vs. positive) and parity (classified into a 3-level variable as first, second and third or greater lactations) as potential predictors of SCH classification. Serum Ca concentration at DIM 4 was a significant predictor of metritis (area under the curve = 0.87; P < 0.01). Cows fed positive vs. negative prepartum DCAD diet were more likely to be classified as SCH at 4 DIM. Parity did not show a significant association with the classification of SCH at 4 DIM. Our results demonstrate the importance of the DIM of blood Ca concentration assessment in connection with the diagnosis of metritis, which is crucial for the most accurate categorization of SCH and the related risk factors.