Introduction: Older adults with preclinical Alzheimer’s disease (AD) show changes in on-road driving performance. The impact of preclinical AD on using automated vehicle (AV) technology is unknown. The aim was to evaluate safety and cognitive workload while operating AV technology in drivers with preclinical AD. Introduction: This cross-sectional study included 40 participants: 19 older adults (age 74.16 ± 4.78; MOCA scores 26.42 ± 2.52) with preclinical AD, evidenced by elevated cortical beta-amyloid; and 21 controls (age 73.81 ± 5.62; MOCA scores 28.24 ± 1.67). All participants completed two scenarios in a driving simulator. Scenario 1 included conditional automation with an emergency event that required a manual take-over maneuver. Scenario 2 was identical but with a cognitive distractor task. Emergency response time was the main safety outcome measure. Cognitive workload was calculated using moment-to-moment changes in pupillary size and converted into an Index of Cognitive Activity (ICA). Mann-Whitney U and independent t tests were used to compare group differences. Results: Emergency response times were similar between drivers with preclinical AD and controls in scenario 1 (20.85 s ± 1.08 vs. 20.52 s ± 3.18; p = 0.83) and scenario 2 (14.83 s ± 7.37 vs. 13.45 s ± 10.43; p = 0.92). Likewise, no differences were found in ICA between drivers with preclinical AD and controls in scenario 1 (0.34 ± 0.08 vs. 0.33 ± 0.17; p = 0.74) or scenario 2 (0.30 ± 0.07 vs. 0.29 ± 0.17; p = 0.93). Conclusions: Older drivers with preclinical AD may safely operate AV technology, without increased response times or cognitive workload. Future on-road studies with AV technology should confirm these preliminary results in drivers with preclinical AD.