ObjectiveTo investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. MethodsA retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. The factors associated with INR>3.0 at the time of discharge were analyzed. ResultsA total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. Multivariate logistic regression analysis revealed that lower body mass index (BMI), preoperative prothrombin time (PT)>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). ConclusionBMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.