Objectives: The majority of motor vehicle occupants who were killed or hospitalized in crashes in Kentucky in 2000–2001 occupied vehicles that were severely damaged in the crash. Even so, overall only a small percentage of all severely damaged vehicle occupants were killed or hospitalized. The purpose was to identify occupant, vehicle, crash, and roadway/environmental factors that were associated with increased risk of severe injury in crashes where the occupant's vehicle was severely damaged. Methods: This study probabilistically linked Kentucky's statewide motor vehicle crash and inpatient hospital discharge data files for 2000 and 2001, and selected cases representing occupants of vehicles that were reported by police as having either “severe” or “very severe” damage. For occupants who were identified through data linkage as having been hospitalized, the Injury Severity Score (ISS) was calculated using ICDMAP-90 TM software, and the scores were stratified into the following categories: critical (> 24), severe (15–24), moderate (9–14), and mild (< 9). We then created an outcome variable, injury severity level, with five levels: killed; hospitalized with at least moderate injuries (ISS = critical, severe, or moderate); hospitalized with mild injuries (ISS = mild); injured according to the police report but not hospitalized; and no apparent injury according to the police report. We performed a stepwise, ordinal logistic regression of injury severity, using independent variables identified from the existing crash literature. Results: Occupant risk factors for higher levels of injury severity selected by the regression were age (risk increased with age, other factors being equal), female gender, restraint non-use, ejection from the vehicle, and driver impairment (by alcohol and/or drugs). Crash risk factors included head-on collision, collision with a fixed object, vehicle rollover, and vehicle fire. Roadway/environmental factors were federal- or state-maintained roadway and posted speed limit 89 kph (55 mph) or greater. Conclusions: Many of the identified risk factors are explicitly or implicitly mentioned in the strategic plans of key organizations involved in highway safety and injury prevention in Kentucky. Our analysis provides additional evidence of their importance, and confirms that their mitigation will reduce injury severity in crashes involving severe vehicle damage. Additionally, older occupants and female occupants showed increased risks of serious injury, but to our knowledge these factors are not currently addressed in any state plans. An opportunity exists to clarify the nature of these risks through further studies, which might lead to the identification of countermeasures specific to these populations.