Objective ·To investigate the association of insulin resistance with left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) in patients without a history of diabetes mellitus. Methods ·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2014 to December 2022. The patients were followed up for 6 months. Age, gender, smoking status, blood pressure, body mass index, biochemical indexes (liver function, kidney function, lipid profiles, glycemic levels and peak troponin levels, etc.) and pharmacological treatment were recorded. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated. Patients were divided into 4 groups (low-level group, low-to-medium-level group, medium-to-high-level group, and high-level group) according to the quartiles of mean HOMA-IR levels. Echocardiography was performed at baseline and during follow-up. Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed. Results ·A total of 219 patients were finally included, with an average age of (62.7±11.9) years, and male patients accounted for 85.4% (187 cases). The average follow-up time was (6.4±1.8) months. During follow-up, the average number of HOMA-IR measurements was (4.32±2.18), and the mean value of visit-to-visit HOMA-IR was 2.41 (1.58, 3.98), which was higher than normal range. The results showed that post-infarction LV end-diastolic diameter (P=0.027) and LV end-diastolic volume index (P=0.013) generally showed a trend for dilation with increasing mean HOMA-IR levels. Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions (Δ LV end-diastolic volume index: r=0.20, P=0.003; Δ LV end-diastolic diameter: r=0.21, P=0.002). Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI, even after adjusting for age, gender, traditional risk factors (history of hypertension, body mass index, smoking status, renal function and lipid profiles), pharmacological treatment, baseline LV ejection fraction and peak troponin levels. Compared with patients with the lowest quartile of HOMA-IR, those with the highest HOMA-IR quartile exhibited a 7.727 mL/m² increase in LV end-diastolic volume index (P<0.001). Conclusion ·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus. Insulin resistance is an independent predictor of adverse LV remodeling in this population.