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To determine efficacy and safety of rituximab treatment as a second-line immunotherapy treatment for autoimmune limbic encephalitis (ALE) and to determine factors associated with functional improvement and favorable outcome following rituximab treatment.We recruited 80 patients with ALE who were treated with rituximab as a second-line immunotherapy from the Korea Autoimmune Synaptic and Paraneoplastic Encephalitis Registry and reviewed 81 patients without rituximab as a control. We grouped patients according to the detection or type of antibodies; in addition, we evaluated clinical, laboratory, first-line immunotherapy, and rituximab treatment profiles and defined main outcomes as improvements on the modified Rankin Scale (mRS) score and a favorable mRS score (0–2) at the last follow-up.Functional improvement occurred more frequently in the rituximab group compared to the control group. In the rituximab group, 30 (37.5%) patients had synaptic autoantibodies, 15 (18.8%) in the paraneoplastic autoantibodies, and 35 (43.8%) were antibody-negative. The effect of rituximab was the same regardless of autoantibody status. Additional monthly rituximab therapy and partial response to first-line immunotherapies were associated with mRS score improvements, as well as favorable mRS scores. mRS scores of 4–6 as the worst neurologic status predicted an unfavorable mRS score. There were no reported serious infusion-related or infectious adverse effects of rituximab.Rituximab is effective and safe as a second-line immunotherapy for ALE, regardless of autoantibody status. Additional monthly rituximab therapy might potentiate the efficacy of rituximab.This study provides Class IV evidence that rituximab improves mRS scores for patients with autoimmune limbic encephalitis who fail first-line therapy.