Roadside safety hardware systems play a vital role in reducing both the number and severity of multi-vehicular collisions by preventing errant vehicles from traversing through an open median into oncoming traffic. The safety hardware used to prevent cross-median crashes are categorized into flexible, semi-rigid, and rigid barriers based on the allowable deflection and energy absorption of the barrier system. Various barrier systems exist in each category and are required to be evaluated using full-scale crash tests prior to installation approval. Although the majority of the barrier systems are only tested using small- and medium-sized passenger vehicles, impact scenarios involving heavy vehicles (i.e., tractor-trailers) should be investigated to further understand the performance limits of barrier systems and create a safer environment for all vehicles on the road. While full-scale crash tests are useful in understanding the post-impact behavior of a vehicle and a barrier system’s redirection capabilities, they are expensive to conduct and are limited by the number of crash scenarios that can be investigated efficiently and effectively. In this research, a finite element model of a full-scale tractor-trailer was improved, validated against full-scale crash test data, and used to simulate crash scenarios on flexible, semi-rigid, and rigid median barriers installed on flat and sloped terrain. The standardized impact conditions and evaluation criteria were utilized for these crash scenarios to assess the median barrier performance, the tractor-trailer post-impact behavior, and the occupant injury risk based on impact severity.