To compare the effectiveness and safety of intravenous immunoglobulin (IVIg) or intravenous methylprednisolone (IVMP) vs and IVIg plus IVMP (IPI) as initial therapy in anti- N-methyl-D-aspartate receptor (NMDAR) encephalitis.A multicenter study of prospectively identified NMDAR encephalitis individuals who presented from October, 2011, to August, 2020, to the study hospitals of western China, with a median follow-up of 3.9 years. Prespecified candidate variables were the prescriptions of IVIg, IVMP, or a combination of both. Propensity score matching was also performed to control potential confounders.A total of 347 NMDAR encephalitis patients were finally analyzed in this study. After the TriMatch for NMDAR encephalitis, 37 triplets were generated. Compared to IVIg or IVMP, the administration of IPI exhibited a significant benefit of a higher response rate (86.5% vs. 55.6% vs. 68.7%, pcorr <0.01); improved mRS score at 3, 6, and 12 months (pcorr <0.05); and reduced further recurrence rate (10 of 37 [27.0%] vs 9 of 37 [24.3%] vs 2 of 37 [5.4%]; p log rank = 0.01). There was no association between treatment superiority and patient sex or the presence of tumors (p≥0.05). Patients treated with IVMP had a significantly higher number of adverse events, but 99% of adverse events were mild to moderate and did not lead to a change in treatment.In patients with NMDAR encephalitis, adequate response, favorable outcome, and less recurrence were each more likely to occur in individuals treated with a combined immunotherapy than in monotherapy individuals.This article is protected by copyright. All rights reserved.