A significant majority of hazardous materials (hazmat) shipments are moved via the highway and railroad networks, wherein the latter mode is generally preferred for long distances. Although the characteristics of highway transportation make trucks the most dominant surface transportation mode, should it be preferred for hazmat whose accidental release can cause catastrophic consequences? We answer this question by first developing a novel and comprehensive assessment methodology—which incorporates the sequence of events leading to hazmat release from the derailed railcars and the resulting consequence—to measure rail transport risk, and second making use of the proposed assessment methodology to analyze hazmat transport risk resulting from meeting the demand for chlorine and ammonia in six distinct corridors in North America. We demonstrate that rail transport will reduce risk, irrespective of the risk measure and the transport corridor, and that every attempt must be made to use railroads to transport these shipments.