Background: Surgical treatment of trigeminal neuralgia (TN) can be highly effective, but durability of pain relief varies and factors influencing surgical failure are poorly understood. We hypothesized that structural brain differences—assessed using magnetic resonance imaging (MRI)—might distinguish surgical responders from early non-responders. Methods: We retrospectively identified 35 TN patients treated surgically from 2005-2017 with high-resolution, -pre-operative MRI scans adequate for quantitative structural analysis. Patients were classified as non-responders if, within 12-months after surgery, they: 1) underwent or were offered another surgical procedure; or 2) reported persistent, inadequately-controlled pain. Volumes of pain-relevant subcortical structures (amygdala, thalamus, and hippocampus) were measured on T1-weighted MRI scans using an automated approach (FSL-FIRST). Results: Surgical responders had significantly larger hippocampi bilaterally compared to early non-responders. Thalamus and amygdala volumes did not differ between groups. Conclusions: Pre-operative differences in brain structure, notably in the hippocampus, may predict durability of response to surgery in patients with TN.