Objective: Road departures are one of the most severe crash modes in the United States. To help reduce this risk, vehicles are being introduced in the United States with lane departure warning (LDW) systems, which warn the driver of a departure, and lane departure prevention (LDP) systems, which assist the driver in steering back to the roadway. Previous studies have estimated that LDW/LDP systems may prevent one third of drift-out-of-lane road departure crashes. This study investigates the crashes that were not prevented, to potentially set research priorities for next-generation road departure prevention systems. Methods: The event data recorder (EDR) data from 128 road departure crashes in the National Automotive Sampling System Crashworthiness Data System (NASS-CDS) from 2011 to 2015 were mapped onto the vehicle trajectory and simulated with LDW/LDP to assess the potential for crash avoidance. The model predicted that 63-83% of single-vehicle road departure crashes may not be prevented by an LDW system and 49% may not be prevented by an LDP system. Results and Conclusions: For LDP systems, which were assumed to have zero latency, no crashes were avoided if the time-to-collision (TTC) from lane crossing to impact was less than 0.55 s. Obstacles such as guardrails and traffic barriers, which tend to be very close to the road, were more common among the remaining crashes. The study shows that LDW/LDP systems are limited by two factors, driver reaction time and TTC to the roadside object. Thus, earlier driver response and longer TTC may help in these situations.