We investigated the efficacy and safety of rivastigmine alone and combined with memantine in Alzheimer's disease patients previously failing on donepezil or galantamine. This was a prospective, open-label, multicentre study. After stopping donepezil or galantamine, patients received rivastigmine 3-12 mg/day for 16 weeks. Non-responders to rivastigmine monotherapy at week 16 received memantine 5-20 mg/day plus rivastigmine for 12 weeks. The primary efficacy parameter was response (Mini-Mental State Examination equal or better than at week 16) to dual therapy at week 28. Secondary criteria were changes on cognitive and behavioural scales. Two hundred and two patients were included. Ninety-three (46.3%) patients responded to rivastigmine monotherapy. Of 86 patients receiving additional memantine for another 12 weeks, 67 (77.9%) responded. Combination therapy caused no apparent safety concerns. When patients fail on donepezil or galantamine, switching to rivastigmine may improve cognition and behaviour. Should they continue to deteriorate, the addition of memantine may be beneficial.