Introduction: It is called as heart failure with reduced ejection (HFrEF) while ejection fraction (EF) is lower than 40%. Patients with EF=40-50% is called as heart failure with mid-range ejection fraction (HFmrEF) which is considered as a subgroup of heart failure with preserved ejection fraction (HFpEF) rather than HFrEF. Angiostatin inhibits the proliferation of smooth muscles, endothelial cells, and mesenchymal stem cells. In this study, we aimed to investigate the clinical significance of angiostatin in HFrEF and HFmrEF patients without chronic kidney disease (CKD). Body text: A total of 62 people consisting of patients with a diagnosis of HFrEF and HFmrEF without CKD (n = 25) and healthy (n = 37) subjects were included in this study. Blood samples were obtained and serum angiostatin, plasma Nterminal Pro-BNP analysis, and transthoracic echocardiography were performed. Results and Discussion: The angiostatin level of HFrEF and HFmrEF group was significantly higher than the control group (94,32 (58,7-282,1); 47,14 (18,8-100,2); p<0.001; respectively). Average angiostatin level of HFrEF and HFmrEF patients using calcium chanel blocker (CCB) was significantly higher than the HF patients without CCB (200,4 (79,1 - 282,1); 83,5 (58,7 - 228,7; p = 0.021; respectively). Average angiostatin level of HFrEF and HFmrEF patients using spironolactone was significantly lower than the HF patients without spironolactone use (61,8 (58,7 - 64,1); 133,8 (62,3 - 282,1); p = 0.027; respectively). Conclusion: Our study is the first study in this area. Angiostatin may be an important marker in HFrEF and HFmrEF patients. Use of spironolactone may induce angiogenesis and apoptosis and CCB may inhibit angiogenesis in HFrEF and HFmrEF patients. Further studies are required on this subject.