Patients with dementia face driving difficulties and, at some point, cease driving. We sought to identify predictors of driving cessation among patients with mild cognitive impairment (MCI) or mild Alzheimer’s disease dementia (AD). We enrolled in this longitudinal study patients with MCI, AD (Clinical Dementia Rating < 2) and cognitively normal (NC) individuals. At baseline evaluation, participants underwent a neurological, neuropsychological and driving simulator assessment. Re-evaluations after 48 and 84 months included a structured interview with the patients and their caregiver. Primary endpoints were driving cessation, death and progression to dementia. 109 individuals were included (32 NC, mean age 65.8 years/47 MCI, mean age 69.1 years/30 AD, mean age 72.8 years). Dangerous driving events during follow-up were referred for 45% and 59% of MCI and AD patients, respectively. 18 MCI (38%, mean time to cease 35 months) and 25 AD (83%, mean time to cease 15 months) patients ceased driving during follow-up. 36% of MCI patients progressed to dementia during follow-up. Cox Regression multivariate analysis revealed age (Hazard Ratio-HR 1.080), semantic verbal fluency-SVF (HR 0.822) and Tandem Walking Test modified with simultaneous reverse number counting-mTWT (HR 1.099) as significant predictors of driving cessation. Simulator accident probability reached statistical significance only in the univariate model (HR 1.040). Age, SVF and mTWT are significant predictors of driving cessation among MCI and AD patients. Driving simulator may be a promising component of driving evaluation. Large-scale studies are prerequisite for the implementation of a multi-disciplinary driving fitness evaluation protocol.