Myocardial injury after noncardiac surgery (MINS) is the most prevalent vascular complication following surgical procedures. Although the revised cardiac risk index (RCRI) is widely used to predict postoperative cardiovascular complications, its predictive accuracy is suboptimal.Considering genetic influences may improve risk prediction. The authors propose integrating polygenic risk scores (PRS) with the RCRI to enhance MINS prediction. Identification of PRS associated with MINS could provide pathophysiological insights.This is a case-control study nested within the Vascular Events in Noncardiac Surgery Participants Cohort Evaluation cohort, including patients aged 45 and above who underwent noncardiac surgery. Daily troponin levels were measured preoperatively and on days 1, 2, and 3 postoperatively. PRS was computed for MINS risk factors using publicly available summary statistics. Logistic regression models were used to assess the association between each PRS and MINS. PRS discrimination was assessed independently and in combination with RCRI.A total of 253 MINS cases were matched with 253 controls, adjusted for age, sex, and limited to individuals of European ancestry (ntotal = 506). The type II diabetes (T2D) PRS (OR: 1.26; 95% CI: 1.00-1.58; P = 0.047) and the HbA1c PRS (OR: 1.26; 95% CI: 1.03-1.54; P = 0.026) were associated with MINS. No other PRS, including those for coronary artery disease, stroke, and lipid biomarkers, showed significant associations.The T2D PRS and the HbA1c PRS were associated with an increased risk of MINS. The findings may reflect the multifactorial pathophysiology of MINS. Larger genetic studies and trials evaluating perioperative glucose management warrant consideration.