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Purpose: To investigate the effect of discontinuing treatment with cholinesterase inhibitors (ChEIs) on drug costs in patients with advanced dementia. Methods: Severe dementia patients receiving ChEI treatment for over 12 months (n = 43) aged over 65 years (mean age = 82.6 ± 7.5 years) were recruited from 8 nursing homes located in Alicante, Spain. ChEI treatment was discontinued in 23 patients. Here, we report the results from a cost-minimization analysis to evaluate the drug costs with a follow-up period of three months. The drug costs were prospectively analyzed based on drug acquisition costs. Results: At the end of the follow-up, the mean monthly drug costs were €52.68 ± 22.48 in the discontinuation group and €122.54 ± 44.74 in the continuation group - a significant difference of means of -€69.86 (95 % CI, -91.24 to -48.48; p = 0.000). The monthly drug cost reduction for the ChEI discontinuation group was €1,533.35. Conclusion: ChEI discontinuation appears to be a possible option for minimizing treatment costs in institutionalized patients with advanced dementia.