AbstractObjective: To determine the effects of clodronate on vitamin D3‐induced hypercalcemia in dogs.Design: Prospective experimental study.Settings: University research laboratory.Animals: Fourteen healthy intact adult male and female mixed breed dogs.Interventions: Dogs received 7.5 mg of vitamin D3/kg of body weight once orally and were randomly assigned to 2 groups of 7 dogs each. Dogs in the saline control group were given intravenous infusions of 150 mL 0.9% NaCl solution 24 hours after vitamin D3 administration. Dogs in the clodronate group were given an infusion of 4 mg/kg of clodronate in 150 mL 0.9% NaCl solution 24 hours after vitamin D3 administration.Measurements and main results: Clinical signs of vitamin D3 toxicosis were evaluated 48 hours after ingestion of vitamin D3. Dogs that were given clodronate had significantly lower serum calcium (Ca), phosphorus (P), urea, and Ca × P values than dogs in the control group on days 4, 7, and 12 after administration. Additionally, alkaline phosphatase activity was significantly lower in the clodronate group compared with dogs in the control group on days 4 and 7.Conclusions: Parenteral administration of clodronate, a biphosphonate compound and osteoclastic activity inhibitor, may be a useful therapy when administered within the first 24 hours after ingestion of toxic doses of vitamin D3.