Background <p>Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a distinct subtype of acute encephalopathy (AE) in children, often leading to various degrees of neurologic sequelae.</p> Methods <p>We conducted a systematic review and individual patient data (IPD) pooled analysis. We identified published case reports and series from six databases and combined them with four AESD patients from our institution. To address potential small-sample bias and data separation, we performed Firth’s penalized likelihood regression analyses to identify the risk factors for poor outcomes in AESD patients. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category (PCPC) scale.</p> Results <p>Among the 87 patients, 48 (55.2%) had favorable outcomes (PCPC ≤ 2) and 39 (44.8%) had unfavorable outcomes (PCPC &gt; 2). Univariate Firth’s penalized likelihood regression analysis identified the following factors associated with unfavorable outcomes: the first seizure duration ≥ 30&#xa0;min (OR = 2.897, <i>p</i> = 0.023), coma following the first seizure (OR = 2.588, <i>p</i> = 0.045) and involuntary movements (OR = 5.155, <i>p</i> = 0.002). Multivariate Firth’s regression analysis confirmed that the first seizure duration ≥ 30&#xa0;min (OR = 3.456, <i>p</i> = 0.020) and involuntary movements (OR = 5.595, <i>p</i> = 0.004) were independent predictors of poor prognosis.</p> Conclusion <p>Early recognition of these factors may help clinicians identify high-risk patients and provide appropriate prognostic counseling.</p>