Abstract Background: Copeptin is used in the differential diagnosis of diabetes insipidus. Different copeptin immunoassays exist but inter-assay comparability is unclear. The aim of this study was to correlate three commercially available copeptin assays and their diagnostic accuracy in the differential diagnosis of the polyuria-polydipsia-syndrome. Methods: Analyzed data include three different studies: repeated copeptin measures of 8 healthy volunteers undergoing osmotic stimulation; copeptin measures of 40 patients hospitalized with pneumonia; osmotically stimulated copeptin measures of 40 patients with polyuria-polydipsia-syndrome. Copeptin was measured using the automated B.R.A.H.M.S. KRYPTOR, the manual B.R.A.H.M.S. LIA and the manual Cloud Clone ELISA assay. Primary outcome was the diagnostic accuracy in the polyuria-polydipsia-syndrome. Results: In total, 150 copeptin measurements were analyzed. In healthy volunteers, there was a moderate correlation for the KRYPTOR and LIA (interrater correlation coefficient (ICC) 0.74; 95%-CI 0.07-0.91), and a poor correlation for the KRYPTOR and ELISA (ICC 0.07; 95%-CI -0.06-0.29), as for the LIA and ELISA (ICC 0.04; 95%-CI -0.04-0.17). The KRYPTOR had the highest diagnostic accuracy (98% (95%-CI: 83-100)), comparable to the LIA (88% (95%-CI: 74-100)), while the ELISA had a poor diagnostic accuracy (55% (95%-CI: 34-68)) in the differential diagnosis of the polyuria-polydipsia-syndrome. Conclusion: The KRYPTOR and LIA yield comparable copeptin levels and a high diagnostic accuracy, while the ELISA correlates poorly with the other two assays and shows a poor diagnostic accuracy between polyuria-polydipsia patients. Redefining cut-off levels for copeptin assays other than KRYPTOR and LIA must take place before their use in the differential diagnosis of diabetes insipidus.