OBJECTIVE To explore the associations among mannose, indexes of insulin resistance (IR) and secretion, and long-term cardiovascular outcomes. RESEARCH DESIGN AND METHODS Fasting mannose was assayed in 1,403 participants, one-half of which had a first myocardial infarction (MI) with either normal glucose tolerance (n = 1,045) or newly detected dysglycemia (i.e., impaired glucose tolerance or type 2 diabetes; n = 358). Regression models were used to explore mannose associations with surrogate indexes of IR/insulin secretion. Multivariate Cox models were used to investigate the independent association between high (higher quartile) versus low (lower three quartiles) mannose and major adverse cardiac events (MACE) (n = 163) during the 10-year follow-up. RESULTS Mannose was independently associated with IR indexes (all P £ 0.001). High versus low mannose was independently associated with MACE (hazard ratio 1.54, 95% CI 1.07–2.20) in the overall population. CONCLUSIONS Mannose might represent a new biomarker able to track early, potentially detrimental glucometabolic alterations independently of glycemic state.