Data from 1,010 lactating lactating, predominately component-fed Holstein cattle from 25 predominately tie-stall dairy farms in southwest Ontario were used to identify objective thresholds for defining hyperketonemia in lactating dairy cattle based on negative impacts on cow health, milk production, or both. Serum samples obtained during wk 1 and 2 postpartum and analyzed for beta-hydroxybutyrate (BHBA) concentrations that were used in analysis. Data were time-ordered so that the serum samples were obtained at least 1 d before the disease or milk recording events. Serum BHBA cutpoints were constructed at 200 micromol/L intervals between 600 and 2,000 micromol/L. Critical cutpoints for the health analysis were determined based on the threshold having the greatest sum of sensitivity and specificity for predicting the disease occurrence. For the production outcomes, models for first test day milk yield, milk fat, and milk protein percentage were constructed including covariates of parity, precalving body condition score, season of calving, test day linear score, and the random effect of herd. Each cutpoint was tested in these models to determine the threshold with the greatest impact and least risk of a type 1 error. Serum BHBA concentrations at or above 1,200 micromol/L in the first week following calving were associated with increased risks of subsequent displaced abomasum [odds ratio (OR) = 2.60] and metritis (OR = 3.35), whereas the critical threshold of BHBA in wk 2 postpartum on the risk of abomasal displacement was >or=1,800 micromol/L (OR = 6.22). The best threshold for predicting subsequent risk of clinical ketosis from serum obtained during wk 1 and wk 2 postpartum was 1,400 micromol/L of BHBA (OR = 4.25 and 5.98, respectively). There was no association between clinical mastitis and elevated serum BHBA in wk 1 or 2 postpartum, and there was no association between wk 2 BHBA and risk of metritis. Greater serum BHBA measured during the first and second week postcalving were associated with less milk yield, greater milk fat percentage, and less milk protein percentage on the first Dairy Herd Improvement test day of lactation. Impacts on first Dairy Herd Improvement test milk yield began at BHBA >or=1,200 micromol/L for wk 1 samples and >or=1,400 micromol/L for wk 2 samples. The greatest impact on yield occurred at 1,400 micromol/L (-1.88 kg/d) and 2,000 micromol/L (-3.3 kg/d) for sera from the first and second week postcalving, respectively. Hyperketonemia can be defined at 1,400 micromol/L of BHBA and in the first 2 wk postpartum increases disease risk and results in substantial loss of milk yield in early lactation.