OBJECTIVE To evaluate the clinical efficacy and safety of akatinol memantine in the treatment of patients with mild to moderate Alzheimer disease (AD). METHODS One hundred patients with diagnosis of possible or probable AD and Mini Mental State Examination total scores between 10 and 26 from 6 centers in two cities of China were randomly divided into two groups: akatinol memantine group (n = 50, given akatinol memantine 5 mg/d in first week, 10 mg/d in second week, 15 mg/d in third week and 20 mg/d from fourth to sixteenth week); donepezil group (n = 50, donepezil 5 mg/d). Different scales were used to evaluated cognitive function (MMSE), activity of daily life and behavior and mood (Blessed-Roth scale) as well as the severity of dementia (GDS). Safety evaluation was conducted every 4 weeks. RESULTS In comparison with the baseline data, there were significant improvements in cognition assessed with MMSE on 16th week in akatinol memantine group (P = 0.000) and donepezil group (P = 0.000) respectively; There also were significant improvements in activity of daily life, behavior and mood assessed by Blessed-Roth scale in akatinol memantine group (P = 0.000) and donepezil group (P = 0.000) on 8th week and 16th week. However there was no improvements in the change of the basic habit of life assessed with the Part II of Blessed-Roth scale (P > 0.05), and nor an improvements in the serious level of dementia assessed with GDS (P > 0.05). In comparison with the data in donepezil group, there were no improvement in the change of MMSE score, Blessed-Roth scale score and GDS score in akatinol memantine group on 16th week (P > 0.05). Mild and transient adverse events were observed in 6% of akatinol memantine group. CONCLUSIONS As a safe and effective medicine, akatinol memantine, which has a similar effect as donepezil for AD, can remarkably improve the cognition, behavior, and mood of AD patients.