Metabolic syndromes associated with insulin resistance are found in approximately 25% of apparently healthy Americans and are risk factors for type 2 diabetes or coronary heart disease. We sought to quantitatively describe a comparable metabolic syndrome in apparently healthy ponies previously diagnosed with pasture laminitis (PL, n = 54), compared to those without previous indications of laminitis (NL, n = 116). Laminitis histories were obtained on 170 Dartmoor and Welsh ponies in one inbred herd maintained on grass-clover pasture. Pedigree analysis has revealed a dominant mode of inheritance for PL, with nutrition playing a key role in its expression. In March 2004 the ponies were gathered, weighed, scored for body condition, and sampled for blood between 0800 and 1000 h. Body condition scores were higher (p = 0.001) in the PL group (6.4 ± 0.1) than the NL (5.8 ± 0.1). Plasma analysis revealed higher (p < 0.001) concentrations of insulin (22 ± 2 and 11 ± 1 μIU/ml in PN and NL respectively) and triglycerides (99 ± 11 and 52 ± 4 mg/dl), lower (p < 0.001) cortisol (5.3 ± 0.3 and 6.8 ± 0.2 μg/dl), and no differences for glucose or non-esterified fatty acids. Statistically validated proxies based on insulin and glucose indicated insulin sensitivity in the lowest reference quintile of apparently healthy horses and pancreatic β-cell response in the highest reference quintile, the combination of results indicating compensated insulin resistance. The data allow the tentative proposal of a diagnostic definition of a pre-laminitic metabolic syndrome (PLMS) with four criteria: Insulin sensitivity (log 100/[insulin]), 0.68 units or lower; Pancreatic β-cell response (log[100(insulin)/(glucose -50)]), 1.52 units or higher: Serum triglycerides, 73 mg/dl or higher; Body condition score, 6 or higher. The tentative cut-offs are based on the total predictive power of each criteria, with each having a predictive power of 70% or higher. This PMLS in healthy ponies is analogous to the pre-diabetic metabolic syndrome in apparently healthy people, and is the first such set of risk factors to be supported by data in horses. By the end of May 2004, 13 clinical cases of laminitis developed in the PL group, none in the NL group (p < 0.0001). These prospective results demonstrate the predictive value of the PLMS and encourage its further development as a means to identify ponies in special need of nutritional management to avoid laminitis.