Although cholinesterase inhibitors (ChEIs) have been proved to help reduce cognitive deterioration in patients with Alzheimer’s disease (AD), their effects on survival remain inconclusive. This study aims to assess the effects of the persistent use of ChEIs on the risk of mortality in patients with AD. This population-based cohort study included 8614 patients having AD with ChEI prescription from 2002 to 2006 and followed until 2010. Kaplan-Meier curves and hazard ratios (HRs) of mortality were estimated in association with ChEI treatment duration and adherence. The average annual mortality rate per 100 person-years was 9.2 for the short-duration group (discontinued < 1 year) and 7.2 for the long-duration group (discontinued ≥ 2 years). Compared to the short-duration group, the long-duration group had a lower mortality (HR = 0.76, 95% confidence interval: 0.69-0.84) and shorter annual inpatient days. But the annual health-care costs did not differ significantly between the 2 groups.