NTSB investigates hundreds of "major" highway accidents per year. Typically accidents with multiple fatalities and at least one of the vehicles being operated for hire. For example NTSB investigated the Schoharie limousine crash where 20 people died.

Graduated drivers license laws for young drivers, age-21 drinking laws, smart airbag technology, rear high-mounted brake lights, commercial drivers licenses, and improved school bus construction standards all came about at least partially due to NTSB recommendations.