Clinical and subclinical cases of periparturient hypocalcemia occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive feeding strategy was investigated by providing the physiologically active vitamin D3 metabolite, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3). A rumen bolus containing tablets of 1,25-(OH)2D3-glycoside extract from Solanum glaucophyllum (SGE) which releases SGE over several days was developed. The aim was to determine whether Primi and Multi cows fed an herbage based diet are susceptible to periparturient hypocalcemia; whether a bolus containing 0 (C) or 500 µg (SGE) of 1,25-(OH)2D3 administered 3-4 days prior to expected calving affects periparturient Ca status of Primi and Multi cows until three weeks into lactation. One C or SGE bolus was applied to 12 Primi and 12 Multi cows in a two-by-two factorial design. Blood and urine were regularly sampled and selected a posteriori from actual calving day (d0), at bolus application, d-2, d0.5, d1, d1.5, d2, d4, d8, d11, d15, d18 and d22 and at bolus application, d0.5 and d2, respectively. Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE increased on d2, indicating regulation of Ca excess. Three Multi-C cows with clinical signs of hypocalcemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased and Ca dropped by 40% in Multi-C between d0.5 and d2, whereas 1,25(OH)2D3 and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Finally, in contrast to Multi, Primi did not show any sign of subclinical hypocalcemia. Prevention of hypocalcemia with one SGE bolus applied 3-4 days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over three lactation weeks.