<p>IgG4-related disease (IgG4-RD) is a rare immune-mediated, fibroinflammatory disease with heterogenous presentations and no standardized treatment recommendations. This study investigates long-term efficacy and safety of current therapeutic strategies with a focus on rituximab. A retrospective analysis was conducted on 24 patients diagnosed with IgG4-RD at a German tertiary center (2010–2020) using the 2020 revised comprehensive diagnostic criteria. Patients were recruited from Rheumatology and Nephrology. Data included organ involvement, laboratory results, histology, treatments, relapses, therapy-related damage, and comorbidities. The cohort included 12 males and 12 females, median age at diagnosis 53 (95%CI 37.0; 61.0) years. Males had more affected organs (2.4 vs. 1.6; p = 0.036) and higher IgG4 levels (&gt;5× upper limit: 33.3% vs. 16.7%; p = 0.036). Immunosuppressive therapy was initiated in 87.5% of patients, with glucocorticoids (GC) universally included. Rituximab was administered to 71.4%, mainly as a 4 x 375 mg/m² regimen (77.3%), with a median follow-up post first rituximab of 51.0 months (95%CI 27.0; 63.0). Adverse events were not more frequent with rituximab compared to other regimens. At last visit, 47.6% were off immunosuppressives and 38.1% remained on GC. Active organ involvement declined, though 16.7% showed organ damage progression. Relapses were frequent (81.0%), but less common upon rituximab initiation (26.7%). This representative IgG4-RD cohort demonstrates that long-term treatment with rituximab as maintenance therapy is generally effective and safe regardless of therapeutic regimen. Despite this glucocorticoid use remains high, highlighting the need for guidelines to standardize the use of glucocorticoids and DMARDs like rituximab in both induction and maintenance therapy.</p>