Objective Influence factors of the stable warfarin dose in the early period after mechanical prosthetic valve replacement were analyzed to guide the anticoagulation therapy for these patients. Methods A total of 288 patients within 6 months after mechanical prosthetic valve replacement in West China Hospital were followed up and registered at outpatient department from July 2012 to April 2014, including basic information (name, sex, age, height, weight, etc.), general clinical data (cardiac function, heart rate, surgery pattern, etc.) and related data about anticoagulation therapy. The target international standardized ratio (INR) range was 1.60 to 2.20 and the acceptable INR was 1.50 to 2.30. The sex, age, height, body weight, body mass index (BMI), body surface area (BSA) and related clinical factors were analyzed to find the relationship with the dose of warfarin. Results Sex was found to have a significant effect on the stable warfarin dose (P<0.05). Women needed a lower stable warfarin dose than men during the early anticoagulation therapy. There was no significant difference in the stable warfarin dose of patients with different ages, rhythms, NYHA classification, surgery pattern and diseases before operation; but the stable warfarin dose was lower in the patients with radiofrequency ablation during valve replacement procedures than the patients with single valve replacement (P<0.05). There was an association between age, height, weight, BMI, BSA and the stable warfarin dose withR2 of 1.2%, 3.2%, 3.5%, 1.1%, 4.2%, respectively and they could explain 6.1% of variability in warfarin dose. Conclusion During early anticoagulation therapy in patients with mechanical prosthetic valve replacement, it is necessary to consider the effects of various preoperative factors, drug factors and demographic factors on warfarin dose. Even though there is an association between age, height, weight, BMI, BSA and the stable warfarin dose, which can only explain 6.1% of variability in warfarin dose, thus cannot guide the postoperative anticoagulation of these patients.