Increasing adoption of clinical decision support systems (CDSS) is driven by evidence that a well-designed system may impact provider behavior, medication safety, and patient outcomes. This study developed a framework to assess the clinical appropriateness of alerts, and applied the framework to alerts designed for patients with acute kidney injury. The authors identified rates of false positive alerts, alert overrides, provider non-adherence, and provider response appropriateness. Using their proposed framework, they advocate for systematic approaches to implementing and evaluating CDSS to optimize alert adherence and minimize alert overrides. A past AHRQ WebM&M commentary discussed integrating CDSS to improve medication safety.