OBJECTIVE To determine effects for 2 IV regional limb perfusion (IVRLP) protocols involving tiludronate on lameness of horses with navicular syndrome. ANIMALS 15 horses with bilateral forelimb navicular syndrome. PROCEDURES Shoeing and anti-inflammatory injection into the distal interphalangeal joint (DIPJ) of both forelimbs (day 0) were performed on all horses. On day 14, horses received 1 of 3 IVRLPs consisting of 0.1 mg of tiludronate/kg (low-dose tiludronate [LDT]; n = 5), 0.2 mg of tiludronate/kg (high-dose tiludronate [HDT]; 5), or saline (0.9% NaCl) solution (placebo; 5); treatments were repeated at days 24 and 34. Lameness severity of both forelimbs was evaluated via subjective evaluation and force plate analysis before and after shoeing on day 0 and at days 14, 34, 60, and 120. Mean subjective lameness score and peak vertical ground reaction force (PVGRF) for the more severely lame forelimb (LFL) and both (combined) forelimbs (CFL) were compared over time. RESULTS For all horses, mean PVGRF for the LFL and CFL was increased at 14 days. No difference in mean subjective lameness score or mean PVGRF was detected within groups at any time. Mean PVGRF of the CFL was higher for the HDT group than the LDT and placebo groups only at 120 days. CONCLUSIONS AND CLINICAL RELEVANCE Use of the tiludronate IVRLP protocols described here provided no further improvement in lameness over therapeutic shoeing and anti-inflammatory injection of the DIPJ in horses with navicular syndrome. However, HDT-treated horses were objectively less lame than LDT- or placebo-treated horses at 120 days.