This study aimed to identify and investigate the contributing factors influencing injury severity in single-vehicle run-off-road (ROR) crashes, which are known for their high severity. The primary objective was to analyze and compare the impact of these factors across three distinct vehicle classes: passenger cars, sport utility vehicles (SUVs), and pickups. A mixed logit model with heterogeneity in mean and variance was developed to analyze the injury severity outcomes in ROR crashes for the three vehicle classes. The model accounted for the potential variations in the impact of contributing factors across different vehicle types. The study revealed several significant variables consistently influencing injury severity across all three vehicle classes. These included driver age, alcohol or drug usage, seatbelt utilization, airbag deployment, higher travel speeds, and the vehicle model year post-2010. Notably, as driver age increased, the impact on changes in injury severity outcomes was more pronounced for pickup drivers compared to those operating passenger cars and SUVs. Among the common findings was the highly effective role of seatbelt usage in mitigating injury severity in ROR crashes. Additionally, passenger cars were associated with increased injury severity, particularly at relatively higher travel speeds exceeding 75 mph when contrasted with SUVs and pickups traveling between 61 and 75 mph. The study highlights the importance of considering vehicle class-specific factors in analyzing injury severity in ROR crashes. Recommendations include further in-depth investigations into distinct factors contributing to injury severity within each vehicle class and utilizing more extensive crash datasets to gain additional insights for enhancing road safety.