Objective  To observe the efficacy and safety of cardiac resynchronization therapy (CRT)  in patients on maintenance hemodialysis (MHD) with advanced heart failure (HF).  Methods  A prospective observational study was conducted. Patients with MHD and advanced HF who met CRT indications and were admitted to the Second Affiliated Hospital of Nanjing Medical University from January 2021 to June 2022 were enrolled. Changes in cardiac function, electrocardiographic parameters, and echocardiographic parameters were observed after CRT implantation, and adverse events were recorded.  Results  A total of 4 patients were included (2 males, 2 females), with a mean age of (62.3±7.9) years, median dialysis vintage of 76.2 (27.3, 179.0) months, and mean follow-up time of (19.7±9.9) months. Compared with preoperative values, the QRS duration shortened from (183.3±26.3) ms to (150.0±13.0) ms; left ventricular end-diastolic diameter decreased from (70.3±10.3) mm to (64.0±11.1) mm; left ventricular end-systolic diameter decreased from (57.8±13.2) mm to (48.8±15.7) mm; E/e‘ ratio decreased from (27.5±9.9) to (20.6±6.5); and median N-terminal pro brain natriuretic peptide (NT-proBNP) level decreased from 167,459.5 (59,645.8, 231,789.0) ng/ml to 81,773.0 (26,151.3, 134,313.0) ng/ml, representing reductions of 18.2%, 9.0%, 15.6%, 25.1%, and 51.2%, respectively. Left ventricular ejection fraction increased from (32.8±7.4)% to (42.3±15.3)%, an increase of 30.0%. According to the New York Heart Association (NYHA) functional classification, 2 patients improved to NYHA class I and 2 to class II. None of the 4 patients could complete the 6-minute walk test preoperatively; among them, 3 achieved an average walking distance of (328.3±138.2) m at 1 year post-surgery. One patient developed bacteremia after surgery.  Conclusion  CRT may help improve cardiac function in MHD patients with advanced HF and has potential to improve quality of life. Its short-term safety in this specific population is acceptable. However, the impact on long-term prognosis requires further validation with larger sample sizes.