Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD etiology.We aimed to investigate the causal effect of adiponectin on CHD risk.We undertook a Mendelian randomization study using data from genome-wide association studies (GWAS) consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22,233 CHD cases and 64,762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63,746 cases and 130,681 controls; ~ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 unit increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95%CI: 0.68; 1.01) in CARDIoGRAM and 0.97 (95%CI: 0.84, 1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null following adjustment for known CHD predictors Conclusions: Overall, our findings do not support a causal role of adiponectin levels in CHD etiology.