AIM: To determine the value of urine osmolality when conducting a test with 3% hypertonic sodium chloride solution, which allows for the differential diagnosis of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was conducted at the (Endocrinology Research Center. The study included 90 patients with polyuria-polydipsia syndrome from September 2021 to September 2023. All patients underwent sequential two tests with osmotic stimulation: 3% hypertonic saline infusion test and a water deprivation test. The final diagnosis was established based on the results of a fluid deprivation test, the patient’s anamnestic data (previous operations, diseases of the hypothalamic-pituitary region, the presence of mental illnesses), MRI data (the presence of a hyperintense signal from the posterior pituitary on T1-weighted images, a detected tumor or infiltrative formation of the hypothalamic-pituitary area, presence of Rathke’s pouch cyst).RESULTS: 48 patients with a final diagnosis of DI and 42 with a final diagnosis of PP were analysed. A cut-off point for urine osmolality during infusion test with 3% hypertonic saline was found: values less than or equal to 377 mOsm/kg support the diagnosis of DI, and values higher than 377 mOsm/kg support the diagnosis of PP. The sensitivity of the criterion is 89%, 95% CI (77%; 97%), specificity — 98% (87%; 100%), PPV — 98% (88%; 100%), NPV — 89% (76%; 96%), accuracy 93% (86%; 98%).CONCLUSION: The proposed criterion for differential diagnosis has comparable diagnostic accuracy in relation to the differential diagnosis of DI and PP, while the safety of the test may be higher.