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Aim: Memantine is the most recently introduced therapy for the treatment of moderately severe to severe Alzheimer’s disease. The aim of this study was to evaluate safety and effectiveness of memantine under normal clinical practice in patients with moderately severe to severe Alzheimer’s disease. Additionally, we assessed the usual prescription guidelines for memantine.; Patients and Methods: Observational, post-authorization, open-labeled, multicentric study, with visits at 1, 6 and 12 months. Memantine effectiveness was assessed through the following scales: MMSE, CGI-S, FAST, ACDS-ADL, NPI-Q Severity, NPI-Q Stress, at 6 and at 12 months.; Results: A total of 95.9% of the 539 recruited patients received at least one dose of the medication (72.6% women; 78.7 ± 7 years). Among the most frequent adverse events were: agitation (1.2%), retches (1%) and hallucinations (0.6%). MMSE mean value decreased from 9.95 ± 4.1 at baseline, to 8.91 ± 5.17 at 12 months (p = 0.0001). Nonetheless, neuropsychiatry symptoms and caregiver stress also decreased (NPQ-I Severity, p = 0.0059, and NPQ-I Stress, p = 0.0169, at 12 months).; Conclusions: Treatment with memantine was safe and effective. An improvement in neuropsychiatry symptoms and care-giver stress was observed after 6 and 12 months.;