Aims To investigate the relationship between peripheral leukocyte dynamics and the outcome of large hemispheric infarction (LHI) patients. Methods Patients with acute LHI admitted to the neuro-intensive care unit of Xuanwu Hospital from 2013 to 2017 were prospectively enrolled and followed up for 6 months after LHI. Results A total of 84 LHI patients were included, 38 patients suffered brain herniation and 20 patients died from stroke. Compared to patients with benign course, LHI patients with fatal outcome showed larger infarcts and more severe brain edema (P < .01), as well as increased WBC and neutrophil counts throughout the first week after stroke (P < .05). Correlation analysis revealed that neutrophil counts on D2 after LHI positively correlated with infarct and edema volumes measured from CT/MRI (R-2 = 0.22 and R-2 = 0.15, P < .01) and negatively correlated with Glasgow Coma Scale (rho = -0.234, P < .05). Patients with D2 neutrophils > 7.14 x 10(9)/L had higher risk of brain herniation [odds ratio (OR) = 7.5, 95% CI: 2.0-28.1, P = .001], and patients with D2 neutrophils > 7.79 x 10(9)/L had a higher risk of death (OR = 5.8, 95% CI: 1.2-27.0, P = .015). Conclusion Early peripheral neutrophil count after stroke relates to infarct size and the fatal outcome of LHI patients, which might help guiding acute LHI management such as reduction of intracranial pressure and potential antiinflammatory therapy in the future.