Background and Objectives: First-line treatment for trigeminal neuralgia (TN) is limited to carbamazepine and oxcarbazepine, and in refractory cases, alternatives are scarce.Lacosamide has been suggested as a valid option. In this study, we describe a series of patients who received oral lacosamide as treatment for TN after first-line drug failure. Methods:In this retrospective descriptive cohort study, we included patients with refractory TN who attended a tertiary center between 2015 and 2021 and were prescribed oral lacosamide after first-line treatment failure. The primary endpoints were pain relief and adverse effects. We secondarily analyzed clinical outcomes and compared responders versus nonresponders in the search for potential predictors of response.Results: Eighty-six patients were included (mean age: 62 [SD 15.6] years; 54/86 [63%] female). The TN etiology was secondary in 16/86 (19%) patients. Concomitant continuous pain was present in 29/86 (34%) patients. The mean number of previous treatments was 2.7 [SD 1.5]. Pain relief was achieved in 57/86 (66%) cases, with 28/86 (33%) patients presenting adverse effects, all of which were mild. No statistically significant differences were observed between responders and nonresponders, but subtle clinical differences suggested potential predictors of response. Conclusion:Lacosamide may be an effective and relatively safe treatment for refractory pain in TN patients after first-line treatment failure.