CONTEXT: Noisy breathing because of respiratory tract secretions (RTS), often referred to as "death rattle," occurs in up to half of all dying patients. Despite a lack of evidence showing benefit compared with placebo, antimuscarinic medications have been used in an attempt to decrease noise associated with RTS and to decrease family distress. OBJECTIVES: The goal of this study was to compare the efficacy of the antimuscarinic medication atropine with that of placebo in reducing noise associated with death rattle. METHODS: Terminally ill adult hospice inpatients who developed noisy breathing as a result of RTS were randomized to double-blind treatment with atropine or placebo. Study drug was given as a single sublingual dose. Noise from breathing was monitored at baseline and at two and four hours. RESULTS: One hundred thirty-seven participants were randomized to atropine or placebo. Reduction in noise score from baseline to two hours after dose occurred in 37.8% and 41.3% of subjects treated with atropine and placebo, respectively (P=0.73). Noise score reduction at four hours occurred in 39.7% and 51.7% of subjects treated with atropine and placebo, respectively (P=0.21). Differences between groups were not significant at either time point. Atropine was well tolerated. Heart rate increased slightly in both groups (+1.1/minute for atropine and +3.1/minute for placebo) but not significantly. CONCLUSION: Sublingual atropine given as a single dose was not more effective than placebo in reducing the noise associated with death rattle.