BACKGROUND: Elevated plasma preprovasopressin (copeptin) levels are associated with cardiovascular complications as well as with an increased risk for type 2 diabetes (T2D). Here, we studied, whether plasma copeptin is related to carotid intima-media thickness (IMT), a measure of early atherosclerosis, and may thus be one explanation for the high cardiovascular risk in T2D. METHODS: Plasma concentrations of copeptin and IMT of the common carotid artery were determined in 1275 participants of the population-based KORA F4 study. We used linear regression models to investigate associations between copeptin levels and IMT. RESULTS: In the whole study group, copeptin levels were not significantly associated with IMT after adjustment for age and sex. Copeptin and IMT were significantly inversely associated after multivariable adjustment in the total cohort (beta = -0.020 mm, 95% CI: -0.037 mm; -0.003 mm), in men (beta = -0.035 mm, 95% CI: -0.061 mm; -0.009 mm) and in study participants with prediabetes (beta = -0.041 mm, 95% CI: -0.078 mm; -0.005 mm) comparing quartile 4 vs. quartile 1. The negative association of copeptin and IMT in men was present after adjustment for age alone. In women and patients with T2D, copeptin was not significantly associated with IMT. CONCLUSIONS: Plasma copeptin was not associated with an increased IMT in our study cohort. In contrast, copeptin levels were related to a lower IMT in men and subjects with prediabetes, suggesting that elevated copeptin concentrations do not exert proatherogenic effects on carotid arteries.