In order to establish a systematic approach to the study on the injuries sustained by motorcycle riders in accidents and the assessment of protective devices fitted to motorcycles, this research develops a computer simulation model of motorcycle-to-vehicle collision model based on multibody kinematics and dynamics using MADYMO (MAthematical DYnamic MOdel). The effectiveness of the motorcycle-to-vehicle crash model is verified using data of 14 full-scale tests. Comparisons between the simulation peak head acceleration results and the full-scale crash tests data demonstrate a satisfactory agreement between them. The simulation results along with the test data indicate that the leg protectors fitted to the motorcycle can induce harmful consequences to the rider head in some configurations, regardless of their aimed protective effects on the rider’s legs. The findings obtained in this study also provide basis for further improvement of the current model.