Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are increasingly prescribed for glycemic control and weight management, but their association with postoperative thrombotic events after total knee arthroplasty remains unclear. We performed a retrospective cohort study using deidentified data from the TriNetX United States Collaborative Network, including adults who underwent primary total knee arthroplasty between December 1, 2006 and June 1, 2025. Patients with prior myocardial infarction, deep vein thrombosis, venous thromboembolism, or pulmonary embolism were excluded. Exposure was defined as a prescription for a GLP-1 RA within 1 year and 1 day before surgery. A 1:1 propensity score match was performed on demographics, relevant comorbidities, and medications, yielding 11,765 patients in each cohort. Outcomes were postoperative myocardial infarction, deep vein thrombosis, venous thromboembolism, and pulmonary embolism. Compared with matched controls, patients prescribed GLP-1 receptor agonists had a significantly lower risk of myocardial infarction (25/11,246 vs 47/11,171; risk ratio [RR] 0.528; 95% confidence interval [CI], 0.325 - 0.858). GLP-1 RA use was also associated with a reduced risk of deep vein thrombosis (74/11,319 vs 103/11,308; RR 0.718; 95% CI, 0.533 - 0.966) and venous thromboembolism (133/11,040 vs 172/11,027; RR 0.772; 95% CI, 0.617 - 0.967). In contrast, no statistically significant difference was observed in the incidence of pulmonary embolism between groups (49/11,352 vs 58/11,382; RR 0.847; 95% CI, 0.580 - 1.238). Overall, preoperative GLP-1 receptor agonist use was associated with a significantly lower postoperative risk of myocardial infarction, deep vein thrombosis, and venous thromboembolism following total knee arthroplasty in this large, nationally representative cohort.
