Objectives <p>Immune-mediated hypertrophic pachymeningitis (HP) is an inflammatory disorder with diverse neurological manifestations. Considering its various etiology and rarity, HP remains a diagnostic challenge. Comparisons of clinical and prognostic profiles across different etiologies remain insufficiently explored. We analyzed the clinical characteristics, treatment approaches, and outcomes of immune-mediated HP patients from a single center in China.</p> Method <p>A retrospective study was conducted at Peking Union Medical College Hospital, analyzing immune-mediated HP cases from December 2003 to September 2021. We evaluated patients’ neurological symptoms, systemic involvement, image findings, and baseline laboratory results, and compared these features among three predominant etiologies: antineutrophil cytoplasmic antibody (ANCA)-related HP, idiopathic HP, and IgG4-related disease (IgG4-RD). The treatment approaches and outcomes were also reviewed.</p> Results <p>The study included 92 patients, 49 (53.3%) male and 43 (46.7%) female. ANCA-related HP was the leading cause of immune-mediated HP (<i>n</i> = 42, 45.6%), followed by idiopathic HP (<i>n</i> = 28, 30.4%), IgG4-RD (<i>n</i> = 12, 13.0%), and other underlying causes (<i>n</i> = 10, 10.9%). Despite different etiologies, similar patterns of cranial nerve and brain region involvement were observed. Large doses of glucocorticoids combined with immunosuppressants were the most common treatment across all etiologies. Kaplan–Meier analysis (mean follow-up time: 4.1&#xa0;years) showed no significant differences in relapse-free survival rates among the three subgroups.</p> Conclusions <p>ANCA-related HP, idiopathic HP, and IgG4-RD HP were the three predominant causes of immune-mediated HP in this Chinese cohort. The three etiologies exhibited similar clinical manifestations, imaging findings, and long-term prognoses, indicating that a standardized management strategy may benefit HP patients regardless of etiology.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> <p><b>Key Points</b></p> <p>• <i>Immune-mediated hypertrophic pachymeningitis (HP) is a rare disorder with diverse etiologies, and research comparing clinical and prognostic profiles across different causes remains limited. </i></p> <p>• <i>This study involved 92 immune-mediated HP patients, comparing clinical characteristics, imaging findings, treatment approaches, and outcomes among ANCA-related, idiopathic, and IgG4-related HP.</i></p> <p>• <i>The three predominant etiologies of HP showed similar clinical features and similar relapse-free survival rates.</i></p> <p>• <i>Regardless of the underlying etiology, HP patients may benefit from a uniform management approach.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>