BackgroundMagnesium sulfate gargle is widely used as an intervention for preventing postoperative sore throat (POST) due to its analgesic effect achieved by inhibiting calcium influx mediated by peripheral NMDA receptors. This study aimed to investigate its optimal dosage following laryngeal mask airway (LMA) ventilation.MethodsA total of 239 patients aged 18–60 years, with ASA grades I-II, who under general anesthesia with laryngeal mask airway intubation were included. Patients were randomized to gargle 30 ml of either normal saline or magnesium sulfate at 10, 20, or 30 mg/kg 10–15 min before anesthesia, with the primary outcome being the incidence of POST assessed in the PACU and at 2, 6, and 24 h postoperatively. The secondary outcomes included LMA ventilation-related parameters and adverse events.ResultsThe incidence of POST under different dosages of magnesium sulfate was 31.7%, 18.3%, 11.9%, and 6.7% in the PACU; 28.3%, 15.0%, 6.8%, and 6.7% at 2 h; 23.3%, 10.0%, 3.4%, and 3.3% at 6 h; and 15.0%, 5.0%, 3.4%, and 1.7% at 24 h postoperatively. As the dosage of magnesium sulfate gargle increased, the incidence of POST decreased (PACU, P = 0.002; 2 h postoperatively, P = 0.002; 6 h postoperatively, P < 0.001; 24 h postoperatively, P = 0.012). The ED90 values of magnesium sulfate gargle for preventing POST in the PACU and at 2 h postoperatively were 22.747 mg/kg (95% CI: 16.524–37.616) and 18.828 mg/kg (95% CI: 12.847–31.396), respectively. No differences were observed in LMA ventilation-related parameters and adverse events across groups.ConclusionThe prophylactic administration of magnesium sulfate gargle can effectively reduce the incidence of POST, with a dosage of 20 mg/kg identified as optimal.