Abstract: Objective To compare the effect of ketamine and magnesium sulfate gargle in preventing sore throat after removal of a double-lumen endobronchial tube. Methods A total of 120 patients with elective thoracoscopic resection of giant bullae in our hospital between June, 2015 and April, 2016 were randomized into group C(control), group K(ketamine) and group M(magnesium sulfate). The patients rinsed their mouths out with 2 ml normal saline in group C, 30 ml ketamine gargle(0.5 mg/kg, dissolved in 5% dextrose water) in group K, and 30 ml magnesium sulfate gargle(20 mg/kg, dissolved in 5% dextrose water) in group M just 15 minutes before the operation. The incidence of sore throat by visual analogue scale(VAS), hoarseness of voice and dysphagia were recorded immediately after extubation(T₁) and then 6 h(T₂), 24 h(T₃), and 48 h(T₄) after extubation. The vocal congestion and/or vocal edema were examined by indirect laryngoscopy at T₂. The levels of TNF-α, IL-6 and IL-10 at T₀(before surgery), T₁, T₂, T₃ and T₄ were tested. Results The incidence rate and VAS of sore throat were significantly lower in group K and group M than that in group C at T₁, T₂ and T₃(P<0.05). The incidence rate and sore VAS of sore throat were significantly lower in group M than that in group K at T₁ and T₂(P<0.05). The incidence rate of hoarseness of voice and dysphagia were significantly lower in group K and group M than that in group C at T₁, T₂ and T₃ time point(P<0.05). The incidence rate of hoarseness of voice and dysphagia were significantly lower in group M than that in group K at T₁ and T₂ point(P<0.05). The incidence rate of vocal congestion and/or vocal edema was significantly lower in group K and group M than that in group C at T₂ point(P<0.05). The incidence rate of vocal congestion and/or vocal edema was significantly lower in group M than that in group K at T₂ point(P<0.05). The levels of TNF-αand IL-6 were significantly lower in group K and group M than that in group C at T₁ and T₂ point. The level of IL-10 were significantly higher in group K and group M than that in group C at T₁ and T₂ points(P<0.05). The level of TNF-α and IL-6 were significantly lower in group M than that in group K at T₁ and T₂ points(P<0.05). Conclusion Either ketamine gargle or magnesium sulfate gargle can effectively reduce the incidence and severity of sore throat after tracheal intubation using a double-lumen endobronchial tube by their anti-inflammatory effects. Comparing with ketamine gargle, magnesium sulfate gargle is more effective.