Road departures account for nearly one-third of all fatal crashes. Lane departure warning (LDW) and lane departure prevention (LDP) have the potential to mitigate the number of crashes and fatalities that result from road departure crashes. The objective of this study was to predict the effectiveness of LDW and LDP in preventing road departure crashes if all vehicles in departure crashes in the U.S. fleet were equipped with either system. A set of 478 road departure crashes extracted from NASS/CDS 2012 were used to formulate a simulation case set. Each of these crashes were than simulated with and without LDW and LDP systems. The LDW system was assumed to alert the driver at the instance the leading wheel touched the lane marking. A steering-based LDP system was assumed to operate in conjunction with LDW (i.e. by alerting the driver of a lane departure) and directly modulate steering wheel angle at the instance the leading wheel touched the lane marking. Four hypothetical LDP designs were evaluated, using typical evasive maneuvering behavior from a lane departure, to be representative of “light”, “moderate”, “aggressive”, and “autonomous” steering. The LDW system was estimated to reduce the number of crashes by 26.1% and the number of seriously injured drivers by 20.7%. In contrast, the light steering to aggressive steering LDP systems were estimated to reduce the number of crashes by 32.7% to 37.3% and the number of seriously injured drivers by 26.1% to 31.2%. The LDP system with autonomous driving characteristics were estimated to reduce the number of crashes by 51.0% and the number of serious injuries by 45.9%. This study shows that LDW and LDP could mitigate a large proportion of crashes and injuries in lane departure crashes. This paper is directly relevant to the design and evaluation of LDW and LDP systems.