Abstract: Objective To evaluate the long-term clinical efficacy and safety of human umbilical cord Wharton's jelly mesenchymal stem cell (WJ-MSC) on ischemic heart failure (IHF). Methods From December 2010 to December 2013, a total of 40 hospitalized ischemic heart failure patients who were successfully revascularized with drug-eluting stents were enrolled and randomly divided into two groups: WJ-MSCs group (n=20) and control group (n=20). WJ-MSC (2×10⁷) were prepared, and patients in both groups had undergone coronary arteriography. Then 10 ml of WJ-MSC (2×10⁷) suspension was slowly injected via previous infarctrelated coronary artery or predominant blood supply artery for heart in WJ-MSCs group, while 10 ml of 0.9% sodium chloride was slowly injected via the same path of patients in control group. Hepatic and renal function parameters, tumor markers and B-type natriuretic peptide (BNP) plasma level were analyzed before and after 6, 12, 18, and 24 months of transplantation. Echocardiography was performed to measure left ventricular ejection fraction (LVEF) and left ventricle end-diastolic volume (LVEDV). The qualityof life and daily activity were evaluated by SF-36 health scale questionnaire and 6-minute walk test (6MWT). The incidences of cardiac death, non-fatal myocardial infarction, revascularization, cerebral infarction and other serious adverse events were recorded during the follow-up of 24 months. Results Compared with before treatment, the LVEF and 6MWD in WJ-MSCs group increased to the highest level at 12 months after transplantation, while the LVEDV and BNP decreased significantly (36.38±6.38)% vs (43.64±9.27)%, (227.2±57.4) m vs (316.7±68.5) m, P< 0.05; (174.45±55.16) ml vs (135.97±34.85) ml and (4 571.8±3 125.8) pg/ml vs (2 434.8±1 963.8) pg/ml, P< 0.05. There was no significant difference in LVEF, LVEDV and BNP at 24 months after transplantation in WJ-MSCs group compared with before treatment (P> 0.05), while the 6MWD increased significantly (P< 0.05). Patients in WJ-MSCs group achieved better outcomes (LEVF, 6MWD, LVEDD and BNP) than control group during the same period (P< 0.05). Compared with before treatment, the physical function and general health in WJ-MSCs group showed an increasing trend during the follow-up of 24 months (P< 0.05); while the score of role limitation decreased at 6 months and 12 months after transplantation (P< 0.05). The physical function and general health in WJ-MSCs group were all better than control group during the same period (P< 0.05). Conclusion WJ-MSC transplantation via coronary can significantly improve the left ventricular function, reduce left ventricular volume, delay or prevent left ventricular remodeling for at least 18 months, and improve the quality of life and daily activity for 24 months in patients with ischemic heart failure with safety and efficacy.