Traumatic cardiac and thoracic aortic injuries are hypothesized to result from rapid deceleration of occupants during a motor vehicle crash. The purpose of this study was to identify potential risk factors for motor vehicle-related cardiac and thoracic aortic (HTA) injury using the Crash Injury Research Engineering Network (CIREN) database. CIREN data were used to test the hypothesis that there is no difference between occupants with HTA injury and occupants with thoracic injury other than the heart or aorta (non-HTA). Occupant variables (restraint use, airbag deployment, Glasgow Coma Scale score, Injury Severity Score, concomitant injuries, driver versus passenger status, height, and comorbidity) and crash variables (principal direction of force, change in velocity, vehicle crush, intrusion, and vehicle type) were compared for these two groups. Odds ratios were used to quantify the potential risk factors for HTA injury compared with non-HTA injury. There were 168 occupants with an HTA injury and 731 with a non-HTA injury. Greater crash severity (based on vehicle crush and change in velocity), improper safety belt use, and lack of safety belt use were significantly associated with HTA injury. Unrestrained occupants had almost three times the chance of having an HTA injury (odds ratio = 2.86; p < 0.05). For restrained drivers, 41.4% of HTA injuries were caused by vehicle interior components. When not protected by both safety belts and air bags, 45.7% of driver HTA injuries were caused by the steering wheel. For passengers, the vehicle interior (armrests, side interior, and B-pillars) accounted for most HTA injuries regardless of safety system status. More than half of all occupants wearing safety belts who sustained an HTA injury were improperly wearing their safety belts. The high mortality associated with cardiac and aortic injuries supports the need to prevent these injuries from occurring during motor vehicle crashes. These results suggest proper use of safety belts is necessary to prevent cardiac and thoracic aortic injuries. However, other important potential risk factors, such as motor vehicle size and crash severity, might continue to present a challenge to motor vehicle safety professionals.