Because peripartal production diseases are prevalent in dairy cows, early recognition is crucial. Several studies reported metabolic variables as risk predictors for subsequent diseases. To improve on-farm testing and application of those methods, the sampling procedure should take into account variation in gestation length. Furthermore, additional variables indicating cows at risk of any production disease should be sought. Therefore, the objective was to characterize differences between cows with and without postpartum production disease (retained fetal membranes, ketosis, hypocalcemia, abomasal displacement, metritis, mastitis) by prepartum measurement of serum nonesterified fatty acid (NEFA) and plasma insulin-like growth factor (IGF)-I concentrations relative to the artificial insemination (AI) that established pregnancy. Blood was collected from 41 Holstein Friesian cows on 235 to 241, 242 to 248, 249 to 255, 256 to 262, 263 to 269, 270 to 276, 277 to 283, and 284 to 290 d after AI. Health status was assessed daily for 3 wk after calving; 25 cows (66%) had at least one production disease. Cows developing postpartum diseases had higher mean serum NEFA concentrations (450 ± 26 μmol/L; mean ± SE) and lower plasma IGF-I concentrations (78 ± 6 ng/mL) prepartum compared with healthy cows (259 ± 19 μmol/L and 117 ± 8 ng/mL, respectively). In conclusion, because of substantial variation among cows in gestation length, blood samples should be collected and studies performed on risk prediction relative to AI rather than expected date of calving. As the somatotropic axis is one of the key regulators of metabolic adaption for onset of lactation, IGF-I might be a useful variable to differentiate between cows susceptible to production diseases and cows that are able to adapt adequately within the transition period and remain healthy.