ObjectiveTo investigate the clinical outcomes and safety of surgery in infants (< 12 months of age) with drug-resistant epilepsy, clarify surgical indications, and select appropriate surgical methods. MethodsThis was a retrospective analysis of infants with drug-resistant epilepsy who underwent epilepsy surgery and were followed up for > 6 months at the Epilepsy Center of Shenzhen Children's Hospital. Clinical data included etiology, seizure type, surgical procedure, preoperative auxiliary examinations, pathological findings, and intraoperative and postoperative complications. Clinical outcomes were assessed based on postoperative seizure frequency, antiseizure medicines (ASMs) use, and neurocognitive development. Intraoperative blood loss, operative duration, postoperative complications, and duration of intensive care were evaluated to assess the safety of epilepsy surgery. Univariate and logistic analyses were performed to explore the factors influencing prognosis. ResultsEpilepsy surgery was performed on 44 infants with drug-resistant epilepsy, including 7 patients who underwent two operations. The age of seizure onset ranged from 1 day to 11 months (median: 1 month, interquartile range (IQR): 0.1–3.8), the disease course was 1–11 months (median: 4 months, IQR: 2–7), and the age at surgery was 6.9±3.6 months. Twenty-three patients underwent hemispherectomy (52.3%), and two underwent subtotal hemispherectomy. Five patients underwent multilobar disconnection, five underwent frontal lobotomy, and the remaining nine underwent focal resection. The surgical duration was 7.5±2 hours. Intraoperative blood loss ranged from 50–1800 ml (median: 275 ml, IQR: 200–500), with all patients receiving an intraoperative blood transfusion of 0.5–6 U (median: 1.5 U, IQR: 1.5–3). The intensive care unit stay was 1–4 days (median: 1 day, IQR: 1–2). The postoperative complication rate was 13.6% (6/44; two cases of hydrocephalus with intracranial infection, two isolated hydrocephalus, and two subdural hematomas). Excluding one child who died of severe lung infection approximately one year after surgery and one child lost to follow-up after surgery, all other cases were regularly followed up for 10 –49 months (median: 30 months, IQR: 16.5–36). After surgery, patients were treated with 0–3 ASMs (median: 1 ASM, IQR: 0–2); 27.9% (12/43) stopped taking ASMs and 51.2% (22/43) had reduced number of ASMs. Engel I was achieved in 76.7% (33/43) of the patients at the last follow-up. In 17 cases with complete developmental quotient follow-up data, the preoperative and postoperative developmental quotient means were 28.8±21 and 43.2±20.1, showing statistically significant differences (p<0.05) SignificanceEpilepsy surgery in infants under 12 months of age is safe and effective. Early preoperative evaluation is crucial for identifying structural lesions and suitable candidates for surgery among infants with drug-resistant epilepsy. The timeliness of surgery is essential for achieving favorable clinical outcomes.