Adiponectin and leptin link metabolic disorders and coronary artery disease (CAD). We analysed their relationship with CAD, classical risk factors and biomarkers in 287 CAD patients (cases) and 477 unaffected family members (controls) selected from the Indian Atherosclerosis Research Study (IARS). Classical risk factors included diabetes, hypertension, dyslipidaemia and obesity markers. Novel biomarkers were measured according to manufacturer recommendations. Adverse clinical events were recorded through telephonic follow-up. Cases showed lower adiponectin levels (4684.62 ± 190.73 ng/ml) than controls (5768.86 ± 152.87 ng/ml) (p=1.58X10(-5)); Leptin levels were higher in affected males (12.47 ± 1.32 ng/ml) than in male controls (9.53 ± 1.19 ng/ml, p=0.017). Adiponectin 1st quartile showed significant protection against CAD in females when compared to 3rd (odds ratio [OR] 0.39, 0.16-0.92, p=0.032) or 4th (OR 0.32, 0.14-0.72; p=0.006) quartile group. Leptin 3rd quartile showed higher CAD risk in males as compared to 1st quartile group (OR 2.09, 1.09-4.01, p=0.028). Subjects with metabolic syndrome showed low adiponectin and high leptin levels. Adipokines showed opposing association trend with lipids, inflammatory and coagulation markers and strong correlation (r=-0.14 to 0.52) with obesity markers. Cases with recurrent event and controls who developed new cardiac event during follow up showed high adiponectin levels (p<0.05). A model that combined adiponectin, leptin and conventional risk factors yielded the best 'C' index (0.890, 0.067-0.912). CAD patients in the top adiponectin tertile showed relatively poor survival curve as compared to the bottom Adiponectin tertile group. In conclusion, our findings strengthen the reported association between low adiponectin, high leptin, obesity-related metabolic disturbances and incident CAD in Asian Indians.