Objective: To provide pilot data for the safety and efficacy of EGb 761 in the oldest-old patients (aged 80 or older). Materials and methods: In a retrospective analysis, we compared treatment outcomes with EGb 761 or donepezil over 12 months in 189 patients aged 80 years or older suffering from Alzheimer’s disease (AD). Results: Over 12 months, there was no significant difference in cognitive decline, measured with the mini-mental state examination (MMSE) score, between donepezil and EGb 761 (p = 0.31). We found more adverse events in the donepezil group. Conclusion: Results suggest similar effects on cognitive symptoms from the use of EGb 761 in the treatment of dementia in AD together with favorable safety compared to donepezil.