Objective: NT-pro-brain natriuretic peptide (NT-proBNP) has been shown to be an accurate diagnostic marker in patients with heart failure (HF). Adiponectin (Adp) levels are increased in HF but its diagnostic value is still uncertain in these patients. The study was designed to investigate the possible association of these markers in non-cachectic patients with newly diagnosed systolic heart failure. Methods: Fifty-seven systolic HF patients and 20 matched controls were enrolled in an observational cross-sectional study. Physical and echocardiographic examinations were performed and serum Adp, NT-proBNP, tumor necrosis factor-alpha (TNF-α) levels were measured. Study variables were compared between the groups. Correlation analyses were done and the diagnostic validity of the markers was compared with ROC analysis. Results: Adp and NT-proBNP levels were significantly higher in HF group (20.19±12.9 vs. 7.65±4.6 μg/mL; p<0.001 and 1051.74±606.2 vs. 222.53±65.6 pg/mL; p=0.002; respectively). TNF-α levels were similar between the groups (2.83±1.8 vs. 2.08±1.2 pg/mL; p=0.582). Correlation analysis showed significant association among Adp and NT-proBNP levels, (r=0.448; p<0.001), and left ventricular ejection fraction (LVEF) values (r=-0.466; p<0.001). The Adp and NT-proBNP showed comparable diagnostic performances with mean [95% confidence interval] areas under the curves of 0.857 (0.771-0.944) and 0.888 (0.815-0.960), respectively. Conclusion: There were significant correlation between Adp levels with NT-proBNP levels and LVEF values but no any association between Adp levels with body mass index values and TNF-α levels in patients with newly diagnosed systolic heart failure. The result may arouse suspicion about the hypothesis, which proposes that Adp levels simply reflects disease severity or cardiac cachexia in patients with HF.