Approximately 20%-50 % of individuals with autoimmune encephalitis (AE) demonstrate suboptimal responses to first-line therapies, leading to persistent neurological deficits and the need for second-line interventions. Although rituximab has shown potential as an alternative treatment in AE, the existing evidence remains insufficient. This study systematically evaluated and meta-analyzed the efficacy of rituximab in AE patients who either failed or exhibited inadequate responses to first-line treatments, aiming to refine and optimize therapeutic strategies for AE.A comprehensive search of PubMed, Embase, and the Cochrane Library databases was conducted, covering studies published up to June 10, 2024. In addition, manual cross-referencing of relevant studies was performed using both subject-specific and free-text terms such as "Rituximab," "Rituxan," "Mabthera," "RTX," "Mab," "Ma," "AE," "encephalitis," "Anti-NMDAR encephalitis," and "autoimmune encephalitis." Data on rituximab's efficacy as a second-line therapy in AE were independently screened and extracted by two researchers. Statistical analyses were conducted using R4.2.1 software to assess the pooled outcomes of the included studies.Analysis of 14 studies involving 277 AE cases revealed an 80 % favorable prognosis rate (0.72-0.89) for rituximab, with superior efficacy in patients under 18 years compared to those over 18 (I2 = 65.9 %, 38.7%-81.0 %; p < 0.01). The prognosis rate for patients under 18 was 0.85 (0.76-0.93), while for those over 18, it was 0.72 (0.56-0.88). Furthermore, a disease duration of ≤180 days correlated with a better prognosis than durations exceeding 180 days, with rates of 0.82 (0.69-0.94) and 0.74 (0.61-0.87), respectively.Rituximab demonstrates an 80 % favorable prognosis rate in AE cases unresponsive to first-line treatments, particularly in patients under 18 or those with disease duration ≤180 days.© 2025 The Authors. Published by Elsevier Ltd.