Objective To evaluate the efficacy of intravenous infusion of lidocaine combined with magnesium sulfate in the treatment of patients with refractory trigeminal neuralgia. Methods A total of 15 patients with refractory trigeminal neuralgia were treated with intravenous infusion of 100 ml of 0.9% sodium chloride solution, 0.1 g of 2% lidocaine solution, and 1.25 g of 25% magnesium sulfate solution for 1 h, once a week. The number of treatment times was determined by the pain relief of the patient and was usually 1 to 3. The Numerical Rating Scale (NRS) for pain was used to assess pain intensity before treatment and at 1 week, 2 weeks, 4 weeks, 2 months, 4 months, and the last follow-up after treatment. Results The mean follow-up time of 15 patients was 19.7 (8 to 35) months. The NRS score was 8.9±0.7 points before treatment, 6.1±1.9 points at 1 week, 2.6±1.3 points at 2 weeks, 2.1±1.7 points at 4 weeks, 2.2±1.6 points at 2 months, 2.1±1.7 points at 4 months, and 2.1±1.8 points at the last follow-up. The patients reported significant pain reduction after treatment (P<0.05). The overall response rates at 1 week, 2 weeks, 4 weeks, 2 months, 4 months, and the last follow-up after treatment were 7%, 100%, 100%, 100%, 100%, and 93%, respectively. The patients showed significantly improved treatment outcomes at all the above time points except for 1 week after treatment (P<0.05). In the course of intravenous infusion, no patients showed any discomfort such as slowing heart rate and falling blood pressure. Conclusions Intravenous infusion of lidocaine combined with magnesium sulfate is safe and effective in the treatment of refractory trigeminal neuralgia.