The research described in this paper analyzed injury severities at a disaggregate level for single-vehicle (SV) and multi-vehicle (MV) large truck at-fault accidents for rural and urban locations in Alabama. Given the occurrence of a crash, four separate random parameter logit models of injury severity (with possible outcomes of major, minor, and possible or no injury) were estimated. The models identified different sets of factors that can lead to effective policy decisions aimed at reducing large truck-at-fault accidents for respective locations. The results of the study clearly indicated that there are differences between the influences of a variety of variables on the injury severities resulting from urban vs. rural SV and MV large truck at-fault accidents. The results showed that some variables were significant only in one type of accident model (SV or MV) but not in the other accident model. Again, some variables were found to be significant in one location (rural or urban) but not in other locations. The study also identified important factors that significantly impact the injury severity resulting from SV and MV large truck at-fault accidents in urban and rural locations based on the estimated values of average direct pseudo-elasticity. A careful study of the results of this study will help policy makers and transportation agencies identify location specific recommendations to increase safety awareness related to large truck involved accidents and to improve overall highway safety.