BackgroundAcute ischemic stroke (AIS) is a common cerebrovascular disease with high mortality. AIS patients in the intensive care unit (ICU) often have severe conditions that require close monitoring and timely treatment. Receptor‐interacting protein kinase 1 (RIPK1) and RIPK3 play important roles in cell apoptosis and inflammation. However, the relevance of serum RIPK1/3 to AIS patients in the ICU has not been clarified.ObjectiveTo explore the correlation of serum RIPK1 and RIPK3 with the prognosis of AIS patients in the ICU.MethodsOne hundred and twenty AIS patients were selected as the research subjects for the retrospective analysis. The subjects were grouped based on the volume of cerebral infarction and the score of the National Institute of Health Stroke Scale (NIHSS) and mRS. The correlation was explored using Pearson analysis. The predictive value was valued using the ROC curve.ResultsThe content of serum RIPK1 and RIPK3 was gradually elevated with increased cerebral infarction volume and the severity of the disease (p < 0.05). Patients with poor prognosis had a higher content of serum RIPK1 and RIPK3 than those with good prognosis (p < 0.05). Serum RIPK1 and RIPK3 levels were positively correlated with infarct volume, NHISS, and mRS scores (p < 0.001). The area under the curve (AUC) of RIPK1 and RIPK3 for predicting the severity of AIS was 0.703, 0.883, and 0.912, respectively. The AUC for predicting poor prognosis of AIS was 0.797, 0.721, and 0.893, respectively. The cooperative detection of RIPK1 and RIPK3 had higher clinical value.ConclusionAIS patients in the ICU had abnormally elevated content of serum RIPK1 and RIPK3, which was closely related to the volume of cerebral infarction, severity, and prognosis. Combined detection of RIPK1 and RIPK3 might help to early identify the severity and evaluate the prognosis, providing a reference basis for clinical doctors to develop treatment strategies.