A systemic approach for identifying potential safety countermeasures and implementing them across groups of locations sharing the same risk characteristics has been developed for pedestrian-vehicle collisions. This study was funded by the California Department of Transportation (Caltrans) to develop methods for identifying sites where there is potential for significant reductions in pedestrian and bicyclist injury. Data collected between 1998 and 2007 from a 16.5-mile section of San Pablo Avenue (SR 123) in the San Francisco East Bay was used as the study area. A database containing all useful crash information was developed and applied to study the spatial patterns, crash types, and location types of pedestrian-related collision. Several data stratifications were investigated to determine appropriate data aggregations for pedestrian safety analysis. Bicycle-related collisions were also included in the analysis to show the differences between pedestrian and bicycle collisions. A systemic approach was developed to identify the systemic hot spots in the transportation system and then recommend countermeasures for systemic implementation across a targeted type of facility.