Objective To evaluate the long-term anticoagulation outcomes of target international normalized ratio (INR) 1.60 to 2.20 and weekly dosage adjustment of warfarin in patients after mechanical heart valve replacement. Methods Outpatients after mechanical heart valve replacement at least 6 months were registered continually from July 2011 to July 2016 in department of cardiothoracic surgery at Zigong No.4 People's Hospital and West China Hospital. There were 1 690 females (70.62%) and 703 males (29.38%) with a median age of 47 years, ranging from 14 to 80 years. All patients were followed up for 6-61 months. Target INR was 1.60 to 2.20 and warfarin dosage were adjusted weekly. Unexpected bleeding, thrombogenesis and thromboembolism, time in therapeutic range (TTR) and fraction of TTR (FTTR) were recorded and calculated to evaluate the outcome of anticoagulation management. Results A total of 2 393 patients with 26 521 INR values were included for data analysis. INR values varied from 0.90-8.39 (1.82±0.45) and required weekly doses of warfarin were 1.75-61.25 (21.72±7.39) mg. TTR of target INR and acceptable INR was 59.38% (1 449 514.0 days/2 441 060.0 days) and 73.57% (1 795 971.0 days/2 441 060.0 days), respectively. FTTR of target INR and acceptable INR were 50.71% (13 450 times/26 521 times), 65.25% (17 305 times/26 521 times). During the follow-up , anticoagulation-related complications included: cerebral infarction in 21 patients (complete recovery in 18 patients, physical activity disorder in 3 patients), cerebral hemorrhage in 4 patients (death in 1 patient, complete recovery in 3 patients), severe gastrointestinal bleeding in 3 patients (completely recovered) and uterine bleeding in 1 patient (surgical removal of the uterus). Conclusion Target INR 1.60–2.20 and warfarin weekly dosage adjustment for patients after mechanical heart valve replacement is reasonable and safe.