Drivers with cognitive impairment are at increased odds for vehicular crashes. Rear-end collisions (REC) are among the most common crash types. We tested REC avoidance in 61 drivers with mild Alzheimer's disease (AD) and 115 elderly controls using a high-fidelity interactive driving simulator. After a segment of uneventful driving, each driver suddenly encountered a lead vehicle stopped at an intersection, creating the potential for a collision with lead vehicle or with another vehicle following closely behind the driver. Eighty-nine percent of drivers with AD had unsafe outcomes, either an REC or an risky avoidance behavior (defined as slowing down abruptly or prematurely, or swerving out of the traffic lane) compared to 65% of controls (P=0.0007). Crash rates were similar in AD (5%) and controls (3%), yet a greater proportion of drivers with AD slowed down abruptly (70% vs. 37%, P<0.0001) or prematurely (66% vs. 45%, P=0.0115). Abrupt slowing increased the odds of being struck from behind by the following vehicle (P=0.0262). Unsafe outcomes were predicted by tests of visual perception, attention, memory, visuospatial/constructional abilities, and executive functions, as well as vehicular control measures during an uneventful driving segment. Drivers with AD had difficulty responding to driving conditions that pose a hazard for a REC. Some cognitive and visual tests were predictive of unsafe outcomes even after adjusting for disease status.