Reasons for performing study: Bisphosphonates, such as tiludronate, are used to normalise bone metabolism via inhibition of bone resorption. Areas of increased bone resorption and formation are typical lesions in a diseased navicular bone. Objectives: To determine if bone remodelling changes occurring in navicular disease may be corrected with therapies regulating bone metabolism. Methods: We designed a double-blind, placebo-controlled clinical trial to compare 2 doses of tiludronate, 0.5 mg/kg and 1 mg/kg bwt administered via daily i.v. injections over 10 days for the treatment of navicular disease. Seventy-three horses, split into 2 subpopulations of recent and chronic cases, were enrolled to be followed-up over 6 months. Of these, 33 recent and 17 chronic cases meeting the selection criteria were maintained in the final efficacy analyses. Clinical examinations were videorecorded and reviewed blindly by an independent expert. Results: Horses treated with the higher dose showed optimal improvement of lameness and return to normal level of activity 2-6 months post treatment. The more recent the onset of clinical signs at the time of treatment, the greater the efficacy. The treatment did not modify the response to extension and flexion tests. The lower dose failed to significantly improve the condition. Conclusions: Tiludronate efficacy is demonstrated in the treatment of navicular disease at the dose of 1 mg/kg bwt. Potential relevance: Our results support the clinical relevance of bone remodelling changes in the outcome of navicular disease.