Background: Vasopressin plays an important role in maintaining volume homeostasis. However, recent studies suggest that vasopressin also may play a detrimental role in the progression of chronic kidney disease. It therefore is of interest to identify factors that influence vasopressin concentration, particularly modifiable ones. Study Design: Cross-sectional analyses. Setting & Participants: Data used are from participants in a large general-population cohort study (Prevention of Renal and Vascular Endstage Disease [PREVEND]). Patients with a missing copeptin value (n = 888), nonfasting blood sample (n = 495), missing or assumed incorrect 24-hour urine collection (n = 388), or heart failure (n = 20) were excluded, leaving 6,801 participants for analysis. Factor: Identification of lifestyle-and diet-related factors that are associated with copeptin concentration. Outcomes: Copeptin concentration as surrogate for vasopressin. Measurements: Copeptin was measured by an immunoluminometric assay as a surrogate for vasopressin. Associations were assessed in uni- and multivariable linear regression analyses. Results: Median copeptin concentration was 4.7 (IQR, 2.9-7.6) pmol/L. When copeptin was studied as a dependent variable, the final stepwise backward model revealed associations with higher copeptin concentrations for lower 24-hour urine volume (P < 0.001), higher sodium excretion (P < 0.001), higher systolic blood pressure (P < 0.001), current smoking (P < 0.001), higher alcohol use (P < 0.001), higher urea excretion (P = 0.003), lower potassium excretion (P = 0.002), use of glucose-lowering drugs (P = 0.02), higher body mass index (P < 0.001), and higher plasma glucose level (P < 0.001). No associations with copeptin concentration were found for C-reactive protein or use of diuretics or nondiuretic antihypertensives. Limitations: The cross-sectional study design does not allow firm conclusions on cause-effect relationships. Conclusions: Important lifestyle-and diet-related factors associated with copeptin concentration are current smoking, alcohol use, protein and potassium intake, and particularly fluid and sodium intake. These data form a rationale to investigate whether intervening on these factors results in a lower vasopressin concentration with concomitant beneficial renal effects. (C) 2015 by the National Kidney Foundation, Inc.