Background Diabetes is one of the major risk factors for coronary artery disease (CAD); hormones implicated in cardiac diseases may play a role in diabetes development. Increased activities of the arginine-vasopressin (AVP) systemwere shown to be associatedwith type 2 diabetes mellitus (T2DM). The aim of this study was to estimate the values of serum copeptin as a predictive biomarker of CAD and to assess the correlation between copeptin and cardiometabolic risk factors in patients with T2DM. Patients and methods The case–control study included 110 patients with T2DM and 80 age-matched and sex-matched control group. All the participants were subjected to B-mode ultrasonography of both common carotid arteries to measure carotid intimamedia thickness (mm), echocardiography, and coronary arteriography. Serum copeptin levels were measured with a new sandwich immunoassay by using a human copeptin enzyme-linked immunosorbent assay kit. Results Patients with T2DM had significantly higher serum copeptin levels (7.64±1.98 pmol/ l) compared with control groups (4.64±1.11 pmol/l). Serum copeptin levels were significantly higher in patients with CAD (8.64±2.55 pmol/l) compared with patients without CAD (6.36±0.86 pmol/l). Interestingly, copeptin was positively correlated with cardiometabolic risks. The area under the curve of serum copeptin levels in differentiating patient with T2DM from control was 0.768 (P<0.001) and differentiating patient with CAD from the nonischemic group was 0.818 (P<0.001). Conclusion The higher serum level of copeptin in patients with T2DM especially in the patient with CAD is strongly correlated with cardiometabolic risk factors. Keywords: arginine vasopressin, coronary artery disease, copeptin, type 2 diabetes mellitus