OBJECTIVE: To analyze the clinical characteristics and treatment options of severe cases of N-methyl-D-aspartate receptor-resistant (NMDAR) encephalitis. RESULTS: All patients presented with abnormal psychiatric behavior, seizures, and decreased level of consciousness; the incidence of involuntary movements, speech disorders/mutilation, memory loss, central hypoventilation, and autonomic dysfunction ranged from 45% to 65%. The percentage of elevated cerebrospinal fluid pressure, white blood cell count, and protein was 42.86%, 60.00%, and 14.29%, respectively. 31.43% of patients had lesions detected by head MRI, which were located in the frontal, temporal, insula, hippocampus, cingulate gyrus, corpus callosum, brainstem, and cerebellar areas. First-line immunotherapy: all patients received 1-7 courses of intravenous gammaglobulin, with a mean of 3 courses; 91.43% of patients received glucocorticoid therapy, of which 54.29% received high-dose methylprednisolone shock therapy; 5.71% received plasma exchange. Five patients (14.29%) received second-line immunotherapy, including rituximab in four cases and intravenous CTX in one case. 15 patients (42.86%) received a long course of immunotherapy. All patients improved with immunotherapy and were transferred from the intensive care unit, with a median ICU treatment period of 46 days and a median hospital stay of 72 days. At discharge, two cases had mRS scores of 5 and the others scored 1 to 4. There were no deaths during hospitalization. The median follow-up time was 17.57 months, and 85.71% of patients had a good outcome (modified Rankin score 0-2), 1 case (2.86%) died two years after discharge, and 11 cases (31.43%) had recurrence of encephalitis during the follow-up period. Conclusion Hormone combined with intravenous gammaglobulin therapy is effective in patients with severe anti-NMDAR encephalitis, and repeat intravenous gammaglobulin and/or methylprednisolone shock therapy may still be effective if the initial effect is not significant.