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Cigarette smokers have a greater risk of respiratory complications during anesthesia compared with nonsmokers. It is not known whether the relative pungency of an inhaled anesthetic further contributes to the smokers’ increased rate of such complications. In the present study, we tested whether the use of a more pungent anesthetic (desflurane) would result in a higher rate of coughing, breath holding, laryngospasm, or desaturation among patients who smoke. We randomly assigned 110 smokers to anesthesia with desflurane (n = 55) or sevoflurane (n = 55), administered via a laryngeal mask airway. Five patients (9%) receiving desflurane and nine patients (16%) receiving sevoflurane coughed (P = 0.39). Most coughing occurred during induction (33%) or emergence (56%), in the setting of airway manipulation and low anesthetic concentration. The rate of breath holding, laryngospasm, and desaturation was similar between those receiving desflurane versus sevoflurane. A retrospective comparison of this cohort of 110 smokers to a previous group consisting of 100 nonsmokers and 27 smokers receiving an identical anesthetic regimen indicates that cigarette smoking, but not choice of anesthetic, places patients at increased risk of respiratory complications.