Objective: To compare the frequency of -11391 G/A promoter gene polymorphism in subjects with metabolic syndrome (cases) and without metabolic syndrome (controls) and to establish a correlation with insulin resistance index (HOMA) in north Indian population. Methods: A total of 528 subjects, 254 controls and 274 cases were recruited and evaluated. Subjects were classified on the basis of NCEP ATP III criteria. Plasma adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotypes were determined by RFLP-PCR. Data were analyzed by Student’s t test, chi-square test and factorial ANOVA followed by Bonferroni test for multiple contrasts. Results The mean WC, SBP, DBP, TC, TG, VLDL, LDL, Insulin, Glucose and HOMA were significantly (p < 0.001) higher while HDL and serum Adiponectin were significantly lower (p < 0.001) in cases as compared to controls. However, the genotypes (GG/GA/AA: 251/3/0 vs. 266/6/2, χ2 = 2.68, p = 0.262) were similar between the two groups. Conversely, - 11391 G/A promoter gene polymorphism showed significant (p < 0.05 or p < 0.01) and positive association with metabolic risk factors (WC, DBP, TG and HOMA). Conclusion: Study concluded that -11391 G/A promoter gene may have association with metabolic syndrome in north Indian population; however, the findings may need further validation on larger sample size on other populations