Objective: Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high‐risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures. Methods: Patients from 2000 to 2020 with seizures and high‐risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow‐up were evaluated. Results: Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1‐IgG (Hu; n = 24, 39%), Ma2‐IgG (n = 14, 23%), and CRMP5‐IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow‐up a median of 25 months after seizure onset. Ongoing seizures at last follow‐up were associated with Ma2‐IgG or ANNA1‐IgG compared to other antibodies (p =.04), highest seizure frequency being at least daily (p =.0002), seizures on electroencephalogram (EEG; p =.03), and imaging evidence of limbic encephalitis (LE; p =.03). Death occurred in 48% throughout the course of follow‐up, with a higher mortality in patients with LE than in those without LE (p =.04). Of 31 surviving patients at last follow‐up, 55% continued to have intermittent seizures. Significance: Seizures in the setting of high‐risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1‐IgG and Ma2‐IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE. [ABSTRACT FROM AUTHOR]