Objective To explore the safety, effectiveness, and mid-term efficacy of total thoracoscopic mitral valvuloplasty (MVP) with chordal replacement (CR) and quadrangular resection (QR) for the treatment of mitral regurgitation (MR), and to provide reference for guiding the development and selection of clinical diagnosis and treatment methods for MR patients. Methods A prospective randomized controlled study was performed to collect patients with MR who underwent MVP at the Department of Cardiovascular Surgery, Leshan People's Hospital from January 2021 to March 2022. They were randomly divided into a CR group and a QR group by using a random number table, and were followed up for 12 months after the operation. The medical history, perioperative data and adverse cardiac endpoint events during the follow-up period were collected. The differences in surgical efficacy between the two groups were evaluated and compared, and the Kaplan-Meier method was used to compare the differences in survival rates between the two groups of patients. Results A total of 100 patients were enrolled. There were 46 patients in the CR group, including 27 males and 19 females with an average age of 49.50±9.23 years; there were 46 patients in the QR group, including 24 males and 22 females with an average age of 49.91±11.48 years. The aortic occlusion time in the CR group was longer than that in the QR group (P<0.05). Other surgical indicators, including total surgical time, extracorporeal circulation time, ventilator-assisted time, ICU hospitalization time, size of the valve ring, concomitant surgery during the same period, and the incidence of perioperative complications were not statistically different between the two groups (P>0.05). The left atrium diameter, left ventricular end-diastolic diameter, left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricular ejection fraction (LVEF) of the two groups before discharge after the surgery were significantly improved compared to those before surgery (P<0.05). There was a statistical difference in LVEF between the two groups before discharge after the surgery (P<0.05). There was no statistical difference in clinical efficacy between the two groups (P>0.05). Kaplan-Meier analysis showed that the overall incidence of exemption from mild and above mitral regurgitation 12 months after the surgery in the CR group and QR group was 84.8% and 89.1%, respectively. According to the log-rank test, there was no statistical difference in the overall survival curve between the two groups (χ2=0.356, P=0.551). Conclusion CR and QR are both safe and effective methods for the treatment of simple posterior MR.