Objectives: The role of a high-flow fistula in cardiovascular morbidity in hemodialysis (HD) patients is very likely under-recognized. In this study, we evaluated the association of high access flow (Qa) on myocardial fibrosis in HD patients. Methods: Intra-access Qa was regularly monitored among 101 chronic HD patients using an ultrasound dilution technique and a high Qa was defined as Qa >2 L/min. Cardiac output (CO) and the cardiac index (CI) were also concomitantly measured. Non-contrast cardiac MRI was performed in 35 patients, and the degree of myocardial fibrosis was assessed by native T1 relaxation times and a potential marker of fibrosis, serum galectin-3. In addition, we compared levels of N-terminal-natriuretic peptide 1 (NT-proBNP), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor alpha (TNF-α) between patient in different Qa groups.  Results: Native T1 relaxation times and galectin-3 levels were much greater in the HD group compared to the control group, which suggests increased myocardial fibrosis under uremic conditions. Among the 101 HD patients, 20 (19.8%) had Qa >2 L/min and they had significantly higher CO, CI, left ventricular mass (LVM), and T1 relaxation times compared to those with Qa ≤2 L/min. In addition, serum galectin-3 as well as NT-proBNP levels were significantly higher in these patients with a high Qa, indicating a close relationship between increased Qa, CO, LVM and myocardial fibrosis. It is interesting that a higher access Qa for myocardial fibrosis was independent of several traditional risk factors as well as serum levels of NT-proBNP and MCP-1. Conclusions: A supra-physiologically high Qa can be a serious risk for myocardial fibrosis in HD patients. Regular intra-access Qa monitoring can be useful for predicting cardiac damage and predicting the risk for a high-output heart failure.