BACKGROUND: Nerve atrophy results in trigeminal nerve (TN) asymmetry detectable by magnetic resonance imaging (MRI) in humans, but similar studies have not been performed in horses with idiopathic trigeminal-mediated headshaking (ITMHS). HYPOTHESIS: Horses with ITMHS show greater MRI-detected trigeminal-nerve asymmetry than controls. ANIMALS: A total of 20 adult horses with ITMHS and six unaffected control horses. METHODS: Retrospective case-control study of the TN cross-sectional area (TNCSA) based on 3-Tesla MRI scans of the equine brain. TNCSA and its side-to-side differences at four defined measurement points were compared within the two study groups using a linear mixed model. Intraclass correlation coefficient analysis was used to evaluate intra-rater repeatability. The primary outcome was side-to-side TNCSA asymmetry, minimizing confounding effects such as body size. RESULTS: Significantly greater TNCSA side-to-side differences (asymmetry of TN) were detected in horses with ITMHS (F = 11.271, p < 0.001). Horses with ITMHS exhibited a 4.1 to 7.6-fold greater TN asymmetry compared to control horses. Absolute TNCSA did not differ significantly between groups but was influenced by body weight. Measurements demonstrated excellent repeatability, and tentative cut-off values could be calculated to discriminate between ITMHS and control horses based on TNCSA asymmetry. CONCLUSIONS AND CLINICAL IMPORTANCE: The asymmetry of the TNCSA in horses with ITMHS indicates unilateral or asymmetric disease of the TN. The present study highlights the value of MRI examinations in ITMHS and could pave the way for targeted therapeutic approaches.