The study was conducted to explore the effects of EGb 761 (Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany) on neuropsychiatric symptoms (NPS) and cognition in patients with mild cognitive impairment (MCI). One hundred and sixty patients with MCI who scored at least 6 on the 12-item Neuropsychiatric Inventory (NPI) were enrolled in this double-blind, multi-center trial and randomized to receive 240 mg EGb 761 daily or placebo for a period of 24 weeks. Effects on NPS were assessed using the NPI, the state sub-score of the State-Trait Anxiety Inventory and the Geriatric Depression Scale. Further outcome measures were the Trail-Making Test (A/B) for cognition and global ratings of change. Statistical analyses followed the intention-to-treat principle. The NPI composite score decreased by 7.0 ± 4.5 (mean, standard deviation) points in the EGb 761-treated group and by 5.5 ± 5.2 in the placebo group (p = 0.001). Improvement by at least 4 points was found in 78.8% of patients treated with EGb 761 and in 55.7% of those receiving placebo (p = 0.002). Superiority of EGb 761 over placebo (p < 0.05) was also found for the State-Trait Anxiety Inventory score, the informants' global impression of change, and both Trail-Making Test scores. There were statistical trends favoring EGb 761 in the Geriatric Depression Scale and the patients' global impression of change. Adverse events (all non-serious) were reported by 37 patients taking EGb 761 and 36 patients receiving placebo. EGb 761 improved NPS and cognitive performance in patients with MCI. The drug was safe and well tolerated.