Nephrogenic diabetes insipidus (NDI) is one of the principal defects leading to polyuria-polydipsia syndrome (PPS). In the absence of other evident causes (drug interaction, electrolytic disorders or inherited disease), obstructive uropathy is the most likely aetiology. Direct arginine vasopressin (AVP) assessment during water deprivation test (WDT) remains the gold standard in PPS differential diagnosis despite well characterised limitations in this procedure. A new WDT method using copeptin as reliable surrogate of AVP is proposed. This case represents the first report of an NDI due to idiopathic urethral stricture in an adult and it would like to be explicative of the importance of a correct differential diagnosis of PPS and of the risk related to a prolonged WDT procedure in a frail patient. A 48-year-old male patient presenting with polyuria and polydipsia lasting one month was diagnosed with NDI. Copeptin values were clearly elevated both at baseline and after osmotic stimulus. WDT was complicated by development of acute kidney injury. Abdomen ultrasound demonstrated bilateral hydronephrosis, trabeculated bladder and a residual urine volume of 819 cc, in presence of normal kidney size and prostatic gland. A cysto-urethrography showed a sub-stenosis of 35 mm involving the membranous urethral tract. The patient underwent to balloon dilatation and urethrotomy with complete restitutio ad integrum. In our knowledge, this is the first report of idiopathic urethral stricture complicated by NDI in adult. PPS workup requires a global medical evaluation by an endocrinologist. In the suspicion of NDI, urinary tract obstruction should be considered. WDT remains a cornerstone in the differential diagnosis of PPS and the availability of biomarkers including copeptin may simplify the diagnostic process.