Background: Vulnerable plaques are the primary cause of acute coronary syndrome (ACS). The association between in-vivo plaque vulnerability and adiponectin levels in ACS still remains to be determined. Objective: The purpose of this study was to investigate the correlation between adiponectin levels and vulnerable plaque features in ACS patients. Methods: We enrolled 107 ACS patients admitted to our institution; 83 with Non-ST elevation ACS (NSTE-ACS) and 24 with ST-elevation myocardial infarction (STEMI). Adiponectin levels were measured in these patients. Coronary angiography and subsequent optical coherence tomography (OCT) analysis of culprit lesions were performed. Results: Adiponectin level was lower in patients with complex angiographic lesions, compared to those with noncomplex lesions (7.13 ± 3.04 vs. 8.94 ± 2.84 μg/ml, P = 0.002). Adiponectin level was lower in patients with plaque rupture (PR), micro-thrombi, and thin cap fibroatheroma (TCFA), compared to those with nonvulnerable features (7.19 ± 2.95 vs 8.79 ± 3.02 μg/ml, P = 0.007 & 7.29 ± 2.97 vs 8.44 ± 3.09 μg/ml, P = 0.04 and 4.76 ± 0.65 vs 9.74 ± 2.35 μg/ml, P < 0.001 μg/ml respectively). There was a significant negative correlation between adiponectin levels and lipid rich plaque extent and maximum lipid arc (r = −0.05, P < 0.001 & r = −0.03, P = 0.03, respectively). However, a significant positive correlation was observed between adiponectin levels and fibrous cap thickness (r = 0.95, P < 0.001). Conclusion: Low adiponectin levels were associated with complex angiographic lesions and vulnerable plaque features in ACS patients, where there was a significant correlation between it and PR, TCFA, and lipid rich plaque