Objective: To evaluate the effect of the standardized follow-up protocol based on telemedicine follow-up system in patients after mechanical heart valve replacement. Methods: A prospective, nonrandomized, controlled clinical trial was performed on 109 patients who underwent mechanical heart valve replacement in the Affiliated Hospital of North Sichuan Medical College from January 2017 to June 2017. They were divided into two groups according to patient's willingness, place of residence and whether have sufficient technical facilities (computer or mobile device connected to the internet), including 56 patients in the control group and 53 patients in the observation group. The control group received routine follow-up guidance, and the observation group received standardized follow-up protocol, which were followed up for 6 months. The patients in the two groups were analyzed with thromboembolism, hemorrhagic event and International normalized ratio (INR) related to anticoagulation therapy during the follow-up period, and the quality of early anticoagulation therapy was evaluated with Time in therapeutic range (TTR), and the satisfaction of the patients with anticoagulation therapy was investigated. Results: There was no significant difference in INR between the two groups during the follow-up period (P >0.05). The TTR of the control group and the observation group was 44.6% (4 516.6 d/10 127.0d) and 54.1% (5 576.1d/10 307 d), respectively, with statistically significant differences (t=-11.273, P < 0.05).There were no significant differences between the two groups in the anticoagulant complications, thromboembolism, hemorrhagic events (P > 0.05). There was significant difference between the observation group and the control group in overall satisfaction with anticoagulation therapy and helpful in answering the patients' questions (Z=6.42, 5.62, P < 0.05), while no statistically significant difference in service attitude to the follow-up period and satisfaction with the guidance that was provided (P > 0.05). Conclusion Standardized follow-up protocol based on telemedicine follow-up system is applied to patients after MHVR surgery, which is conducive to improving the quality of anticoagulant therapy and improving the satisfaction of patients, and providing reference for the development of "Internet + medical" mode in China.