Objectives We sought to assess whether hyperinsulinemia is associated with percentage lipid and coronary plaque burden in nondiabetic patients with acute coronary syndromes (ACS). Background Hyperinsulinemia carries an increased risk of cardiovascular disease even in pre-diabetic patients, but the precise mechanisms of its effects remain unclear. Methods Nonculprit coronary lesions associated with mild-to-moderate stenosis in 82 nondiabetic patients with ACS were examined by integrated backscatter intravascular ultrasound (IB-IVUS), using a 40-MHz intravascular catheter. Conventional IVUS and IB-IVUS measurements from the worst 10-mm segment (1-mm intervals) were calculated. All patients underwent a 75-g oral glucose tolerance test (OGTT) to calculate the area under the insulin concentration-time curve (AUC insulin) from 0 to 120 min. Results Patients in the high tertile of AUC insulin had a significantly greater percentage lipid area and absolute lipid volume than did patients in the intermediate and low tertiles (tertile 3 vs. tertile 2 vs. tertile 1; 37.6 ± 16.6% vs. 25.8 ± 11.9% vs. 27.5 ± 14.7%, p < 0.01 by analysis of variance ANOVA, and 29.9 ± 22.6 mm3 vs. 15.3 ± 12.6 mm3 vs. 17.7 ± 12.7 mm3 , p < 0.01 by ANOVA, respectively) and a smaller percentage fibrosis area (55.0 ± 11.5% vs. 61.7 ± 9.4% vs. 60.7 ± 9.4%, p = 0.03 by ANOVA). Multiple regression analysis showed that the high tertile of AUC insulin was independently associated with an increased percentage lipid area (p < 0.05). On conventional IVUS analysis, external elastic membrane cross-sectional area was significantly increased with greater plaque volume in patients in the high tertile of AUC insulin (both p < 0.05 by ANOVA). Conclusions Hyperinsulinemia is associated with an increased lipid content and a greater plaque volume of nonculprit intermediate lesions in nondiabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.