The Office of Safety of the Federal Railroad Administration (FRA) is responsible for ensuring public and personnel safety in U.S. railroad operations. This office ensures the safe rail transportation of hazardous materials by conducting inspections of railroad operations and equipment, including tank cars, and developing safety-related regulations. In the past few years, the Office of Safety has been using risk analysis as a tool in making rational regulatory decisions on hazardous materials transportation in tank cars. A risk analysis protocol developed by FRA is described to evaluate the risks to the U.S. population arising from the transportation of different types of chemicals in tank cars on the U.S. railroad system. Following several recommendations of the National Transportation Safety Board requiring the shipment of several hazardous chemicals in highly protected, pressure-rated tank cars rather than in the minimum packaging authorized by the Code of Federal Regulations, a risk-based evaluation was made on the effect of implementing these recommendations on the overall risk reduction. The risk results were presented in the parameters of Military Standard 882-B. Policy decisions were made based on the results.