Pasture-based Holstein-Friesian cows from three genetic groups differing in the Irish 'Economic Breeding Index' (EBI) value and genetic background, namely North-American (NA) national average EBI genetic merit (LOW-NA, n = 42), North-American high EBI genetic merit (HIGH-NA, n = 42) and New Zealand (NZ) high EBI genetic merit (HIGH-NZ, n = 42), were studied. These genetic groups have been selected in different environments: pasture for NZ and confinement for NA. The objective was to determine the effect of genetic group on haematological and acute phase proteins profiles (white blood cell (WBC) counts, red blood cell (RBC) counts, acute phase proteins: serum amyloid A (SAA) and haptoglobin), health (rectal temperature (RT), clinical mastitis (CM) and somatic cell score), calving performance (stillbirth, calving assistance) and post-partum reproductive parameters (endometritis and ovarian cyclicity). Blood sampling and data recording took place 3 weeks pre-calving up to 7 weeks post-calving. Linear mixed models, logistic regression and generalised estimating equations were used for data analysis. HIGH-NZ animals had the highest (P < 0.05) RBC mean corpuscular volume (50.0 fl), exhibited a different WBC distribution pattern (P < 0.05) and had the lowest (P < 0.05) mean RT (38.4°C) for the first 10 days post-calving. These findings suggest enhanced reticulocyte turnover, peripartum response mechanisms and thermoregulation in the HIGH-NZ compared to the other two genetic groups. LOW-NA animals had the highest SAA peak throughout the peripartum period (55.12 mg/l, P < 0.05) and a tendency for higher somatic cell scores (P < 0.10) in early lactation. The HIGH-NA animals had the lowest incidence of udder quarter milk sample bacteria at calving, suggesting better udder health when commencing lactation. No differences were detected between genetic groups in calving performance, post-partum reproductive parameters or CM in the first 42 days post-calving. These results suggest that while inherited peripartum adaptation strategies have been developed by the different genetic groups selected in different environments (pasture = NZ v. confinement = NA), such differences have minimal impact on peripartum clinical health.