Enabling clinical decision support (CDS) across multiple electronic health record (EHR) systems has been a desired but largely unattained aim of clinical informatics, especially in commercial EHR systems. A potential opportunity for enabling such scalable CDS is to leverage vendor-supported, Web-based CDS development platforms along with vendor-supported application programming interfaces (APIs). Here, we propose a potential staged approach for enabling such scalable CDS, starting with the use of custom EHR APIs and moving towards standardized EHR APIs to facilitate interoperability. We analyzed three commercial EHR systems for their capabilities to support the proposed approach, and we implemented prototypes in all three systems. Based on these analyses and prototype implementations, we conclude that the approach proposed is feasible, already supported by several major commercial EHR vendors, and potentially capable of enabling cross-platform CDS at scale.