BACKGROUND: Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses.OBJECTIVES: To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses.ANIMALS: Forty-nine healthy, university-owned adult lightbreed horses.METHODS: Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/kg PO q24h, n = 7) of meloxicam for 2 weeks, compared with control horses (placebo, n = 7, or phenylbutazone, 4.4 mg/kg q12h on day 1, 2.2 mg/kg q12h for 4 days, then 2.2 mg/kg q24h for 9 days, n = 5).RESULTS: Maximum plasma concentration following a single oral dose of meloxicam was 915.1 ± 116.9 ng/mL and elimination half-life 10.2 ± 3.0 hours. Meloxicam (0.6 mg/kg, q24h, PO for 6 weeks) yielded plasma concentrations between 100 and 1000 ng/mL and was well tolerated by healthy adult horses. Administration of 3-5 times the recommended dose of meloxicam was associated with decreased total serum protein and albumin concentrations, gastrointestinal damage, renal damage, or bone marrow dyscrasia. PBZ administration was associated with the development right dorsal colitis, gastric ulceration, and protein losing enteropathy in 2 horses.CONCLUSIONS AND CLINICAL IMPORTANCE: Administration meloxicam at 0.6 mg/kg q24h was well tolerated for 6 weeks, without drug accumulation in plasma. Higher doses were associated with dose-dependent adverse effects typical of class of drugs.