ABSTRACT: Accessibility-related research has advanced considerably since its foundational conception six decades ago. Yet, despite widespread acceptance of the concept, these methods are still rarely used in practical applications among transportation agencies and policymakers. Until recently, the challenges were mainly technical but now they are more practical. Practitioners are often faced with decisions about appropriate methods and metrics, which are difficult to answer from the current literature. This study attempts to produce a clearer understanding of the effects that those decisions have on practical outcomes, based on data spanning many geographies across the U.S. We test a variety of metrics—including different modes, destination types, analytical geographies, and metric definitions—in regions spanning seven states. This study points to several potential best practices, including the use of non-work walking accessibility metrics in multimodal analysis and the use of decay functions in accessibility metrics, and provides a strong foundation for future research.