Cardio-renal disease is a common clinical condition leading to increased morbidity and mortality. Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are the cornerstone of treatment of chronic cardio-renal disease. Using data from the REPOSI register, we performed a multicenter, observational, retrospective study to determine which factors are associated with the non-prescription or discontinuation of ACE-Is/ARBS in a cohort of 889 cardio-renal patients hospitalized in 109 Italian internal medicine and geriatric wards. Only 55% of the patients with cardio-renal disease of the investigated cohort were on treatment with ACE-Is or ARBs at admission. The primary end point was ACE-Is/ARBs use at discharge. Patients with lower probability of receiving ACE-Is/ARBs at discharge were older and hospitalized for longer periods. Furthermore, patients with advanced chronic kidney disease (advanced CKD: eGFR ≤ 29 mL/min/1.73m²) had a much lower (54%) probability of being discharged or continuing ACE-Is/ARBs treatment than those with eGFR ≥ 60 mL/min/1.73m². A more prominent lower probability was found comparing advanced CKD patients with G3 stage CKD patients (eGFR: 59-30 mL/min/1.73m²) in multivariate analyses (OR and 95%CI: 0.37, 0.24-0.57. multivariate p-value < 0.001). The probability of stopping treatment in patients already on treatment with ACE-Is/ARBs at hospital admission (secondary end point) almost reached a threefold increase (OR and 95%CI: 2.82, 1.69-4.71. multivariate p-value < 0.001) when the advanced CKD group was compared with G3 CKD patients. The data of our study are not in line with the recently published updated KDIGO 2024 Guidelines, which recommend patients with advanced CKD to continue treatment with ACE-Is/ARBs.