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Objective: Opposite-direction crashes can be extremely severe because opposing vehicles often have high relative speeds. The most common opposite direction crash scenario occurs when a driver departs their lane driving over the centerline and impacts a vehicle traveling in the opposite direction. This cross-centerline crash mode accounts for only 4% of all non-junction non-interchange crashes but 25% of serious injury crashes of the same type. One potential solution to this problem is the Lane Departure Warning (LDW) system which can monitor the position of the vehicle and provide a warning to the driver if they detect the vehicle is moving out of the lane. The objective of this study was to determine the potential benefits of deploying LDW systems fleet-wide for avoidance of cross-centerline crashes. Methods: In order to estimate the potential benefits of LDW for reduction of cross-centerline crashes, a comprehensive crash simulation model was developed.