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In patients with Huntington’s disease (HD), instrumental daily activities such as working and driving become affected at a relatively young age. For most patients, the decision to quit driving is difficult and affects their independence and social activities.To investigate if differences in driving performance between HD gene carriers and healthy individuals can be detected with a driving simulator. Furthermore, we wanted to determine which cognitive and motor symptoms contribute to driving performance in HD.We included 58 HD gene carriers (28 premanifest HD, 30 manifest HD) and 29 controls in this cross-sectional study. All participants were active drivers and underwent neuropsychological, motor, and psychiatric evaluations. A driving simulator, including an urban and motorway scenario, was used to assess driving performance.Manifest HD drove slower compared to controls and premanifest HD when speed limits increased (80 and 100 km/h) and they had a less steady speed compared to premanifest HD on the motorway and in a 30 km/h zone. Manifest HD also had a larger standard deviation of the lateral position (i.e., more weaving of the car) compared to controls and premanifest HD on the motorway. Postural instability and slower speed of processing were predictors of the driving simulator outcome measures. There were no significant differences between premanifest HD and controls.Manifest HD drive more cautious in a driving simulator when speed limits increase compared to premanifest HD and controls and they have less vehicle control on the motorway. Increased postural instability and slower speed of processing are predictive of worse driving simulator performance in manifest HD. This might assist clinicians in their referral for an official on-road driving test. More studies are necessary to determine if a driving simulator can be used to monitor longitudinal changes in fitness to drive.