Abstract Acute Kidney Injury (AKI) in the US has increased by 38% over the last eight years, with drugs as a major contributor to AKI in hospitalized patients. Drug-associated AKI (D-AKI) results in severe consequences with approximately 40% of patients experiencing in-hospital death or dialysis dependence and 70% having evidence of residual kidney damage following the initial D-AKI event. We have determined that many patients at high risk for AKI are identified late and often continue to receive nephrotoxic drugs until AKI becomes severe. Thus, we designed a proposal to address the need for early, appropriate management of nephrotoxins in high-risk patients by studying the effect of an advanced clinical decision support system (CDSS) for primary physicians and hospitalists aimed at reducing D-AKI in hospitalized adults. Specifically, we aim to 1) optimize the clinical performance of D-AKI risk-alerts generated by a clinical decision support system; 2) test whether an advanced clinical decision support system coupled with a pharmacist-led intervention improves short and long- term outcomes for patients with D-AKI; and 3) determine physician perception of the pharmacists’ performance, physician acceptance and cost-effectiveness of our intervention. In 2012 Kidney Disease Improving Global Outcomes (KDIGO) published the first comprehensive AKI clinical practice guideline. Recommendations include the use of standard criteria for defining and staging AKI and a series of stage-based management steps to be considered for all patients with AKI or at risk for developing it. However, clinicians have been slow to adopt these recommendations and some groups (most notably the US KDOQI expert panel), while endorsing the guideline overall, have called for more research testing the recommendations. Our proposal directly addresses this concern by testing whether a unique clinical decision support system identifying high risk patients coupled with an advanced pharmacist service directed to the primary physician can address D-AKI and drug dosing for other forms of AKI to improve patient care. Thus, our central goal is to examine the effect of a pharmacist-led intervention on the early detection and management of AKI, progression of and short-term recovery from AKI, and on various AKI-related outcomes.