Polypharmacy is common in the elderly due to multi-morbidity and interventions. However, the temporal association between polypharmacy and renal outcomes is rarely addressed and recognized. We investigated the association between cardiovascular (CV) polypharmacy and the risk of acute kidney injury (AKI) in elderly patients. We used the Taiwan National Health Insurance PharmaCloud system to investigate the relationship between cumulative CV medications in the 3 months before admission and risk of AKI in the elderly at their admission to general medical wards in a single center. Community-dwelling elderly patients (>60 years) were prospectively enrolled and classified according to the number of preadmission CV medications. CV polypharmacy was defined as use of 2 or more CV medications. We enrolled 152 patients, 48% with AKI (based upon Kidney Disease Improving Global Outcomes [KDIGO] classification) and 64% with CV polypharmacy. The incidence of AKI was higher in patients taking more CV medications (0 drugs: 33%; 1 drug: 50%; 2 drugs: 57%; 3 or more drugs: 60%; P=0.05) before admission. Patients with higher KDIGO grades also took more preadmission CV medications (P =0.04). Multiple regression analysis showed that patients who used 1 or more CV medications before admission had increased risk of AKI at admission (1 drug: odds ratio [OR]= 1.63, P=0.2; 2 drugs: OR=4.74, P=0.03; 3 or more drugs: OR= 5.92, P =0.02), and that CV polypharmacy is associated with higher risk of AKI (OR 2.58; P = 0.02). Each additional CV medication increased the risk for AKI by 30%. We found that elderly patients taking more CV medications are associated with risk of adverse renal events. Further study to evaluate whether interventions that reduce polypharmacy could reduce the incidence of geriatric AKI is urgently needed.