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Insulin resistance (IR) is a key feature in the development of numerous metabolic diseases. The cornerstone for treatment for IR remains diet and exercise, however these have poor rates of adherence. Beta-hydroxy-beta-methylbutyrate (HMB) is a nutraceutical with contentious effects on IR in animal models. The aim of this study was to evaluate the impact of acute HMB on IR in humans during an oral glucose tolerance test (OGTT). Young and older male volunteers underwent two 75 g OGTT with or without 3 g HMB. In young men, HMB significantly reduced the insulin area-under-the-curve (AUC), with no difference in glucose AUC, resulting in a numerical increase in the Cederholm index of insulin sensitivity. In older men, HMB had no effect on insulin or glucose responses. In conclusion, acute HMB may improve IR following a glucose load in young men; however, this does not appear to be sustained into older age., Competing Interests: The authors declare no conflicts of interest. JAR is an employee of Metabolic Technologies Inc., who supplied the free acid-HMB on a collaborative basis. Metabolic Technologies Inc., has patents pending on HMB-FA, and market HMB to nutrition companies., (© 2020 The Authors.)