The acetylcholinesterase inhibitor donepezil hydrochloride improves cognitive function in patients with Alzheimer's disease and vascular dementia. Given acetylcholine's important actions on the heart, we undertook a retrospective cohort investigation to assess whether donepezil usage affects cardiovascular mortality. In patients treated with donepezil, hazard ratios for total and cardiovascular mortality were 0.68 (P = 0.045, 95% confidence interval 0.46-0.99) and 0.54 (P = 0.042, 95% confidence interval 0.30-0.98), respectively. The apparent survival benefit in donepezil-treated patients should not be overinterpreted. Prospective clinical trials are warranted.