Objective <p>To explore the role of serum IgE in IgG4-related ophthalmic disease (IgG4-ROD) by comparing clinical features and prognosis of patients with elevated and normal serum IgE levels.</p> Methods <p>This single-centre retrospective study included 54 IgG4-ROD patients diagnosed by histopathology from March 2022 to March 2024. Clinical features of the IgE+ group (serum IgE levels &gt;165 IU/ml) and the IgE− group (serum IgE levels ≤ 165 IU/ml) were compared, and 50 patients were followed for at least 6 months to assess the prognosis. Statistical analyses included t tests, Mann–Whitney U, chi-square tests, Spearman correlation, Kaplan-Meier survival curves, and Cox regression.</p> Results <p>Among the 54 patients, both the IgE+ (n = 22) and IgE− groups (n = 32) were predominantly middle-aged women. Extraocular muscle involvement was more common in the IgE− group (P = 0.033), whereas bilateral ocular (P = 0.040) and sinus involvement (P = 0.046) were more frequent in the IgE+ group. Significant intergroup differences were observed in serum IgG4 (P = 0.004), C1q (P = 0.021), IL-10 levels (P = 0.030), IgG4/IgG (P = 0.022), and IgE/IgG4 ratios (P = 0.018). Serum IgE correlated positively with IgG4, IL-6, IL-10, and IL-12p70, and negatively with C1q and IgM (P &lt; 0.05). The IgE+ group had a higher relapse risk (P = 0.038). Cox regression analysis identified serum IgE as an independent risk factor for relapse (P = 0.022).</p> Conclusion <p>Elevated serum IgE in IgG4-ROD is associated with more severe disease and higher relapse risk, highlighting its potential as a prognostic marker.</p>