Using interview data and blood samples collected at baseline from the Southern Community Cohort Study, this cross-sectional study examined serum adiponectin levels in relation to select environmental and behavioral factors. Several single nucleotide polymorphisms (SNPs) in three adiponectin-related genes (ADIPOQ, ADIPOR1, and ADIPOR2) were also examined in relation to adiponectin and body mass index (BMI). Multivariate linear regression models were used to evaluate the association between adiponectin and BMI separately for white and black women. Prediction models for adiponectin for black and white women were also developed using multiple linear regression. Associations between SNPs in ADIPOQ, ADIPOR1, and ADIPOR2 in relation to adiponectin and BMI were examined in linear regression models with adjustment for age and percentage of African ancestry to account for population stratification. Black women were found to have lower adiponectin levels compared with whites even after adjustment for body mass index (BMI). These results expand upon previous studies that were limited by small sample sizes or narrow age and body size ranges and demonstrate that racial differences in adiponectin exist across the spectrum of BMI. In the examination of predictors of adiponectin beyond BMI, the factors age, HDL-cholesterol, and hypertension were found to be strong correlates of adiponectin in both race groups. In the genetic analyses, one SNP (rs17366568) in ADIPOQ was found to be significantly associated with adiponectin in white women but not in black women. This finding confirms results from two recent genome-wide association studies in European whites by demonstrating significant differences in adiponectin levels across genotypes of SNP rs17366568 and expands the current literature by examining this SNP in black women for the first time. No significant associations were observed between any of the SNPs in the three adiponectin-related genes and BMI. Observed racial differences in adiponectin and its correlates from this study will be utilized in future studies of diseases potentially affected by adiponectin such as cancer, cardiovascular disease, and type 2 diabetes. In addition, the development of lifestyle interventions as well as therapeutics that increase adiponectin levels for the purpose of disease prevention may be guided by results of this study