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Motor vehicle crashes result in thousands of deaths and millions of injuries each year in the United States (US). To help prevent these injuries and deaths, the National Highway Traffic Safety Administration (NHTSA) and the Insurance Institute for Highway Safety (IIHS) conduct crash tests, which are designed to ensure a minimum level of safety for all vehicles. To gain information on real-world injury patterns and vehicle crashworthiness, multiple research groups sponsored by the NHTSA are designed to collect crash, vehicle, and occupant data from crashes occurring in the US. The Crash Injury Research and Engineering Network (CIREN) and the National Automotive Sampling System - Crashworthiness Data System (NASS-CDS) are two real-world crash databases. The objective of this research was to develop and analyze methodologies and similarity scoring systems to compare crashes. Using CIREN, case-by-case comparisons were achieved to study similarity to crash tests and analyze new safety systems. This research showed that side and knee bolster airbags reduce injury severity for specific body regions in real-world motor vehicle crashes. Mahalanobis scoring revealed that NASS-CDS cases were most similar to FMVSS 214 crash tests and were least similar to IIHS frontal crash tests. Overall, this work provided novel methods for evaluating vehicle crashworthiness and analyzing safety systems to mitigate injuries occurring in motor vehicle crashes.