Objective To explore the impact of a stepwise analgesia and sedation nursing strategy guided by multimodality neuromonitoring（MMM） on intracranial pressure（ICP） changes and prognosis after decompressive craniectomy in patients with large-area cerebral infarction. Methods A total of 84 patients with large-area cerebral infarction who underwent decompressive craniectomy and were admitted to the neurology ICU of a tertiary hospital in Changchun from January 2022 to December 2024 were selected by convenience sampling and randomly divided into a control group and an experimental group using block randomization. The control group received conventional analgesia and sedation，while the experimental group adopted a stepwise analgesia and sedation nursing strategy guided by MMM. The average ICP within 7 days after surgery，the proportion of time within 72 hours that ICP reached the target，mechanical ventilation time，ICU stay，Barthel lndex at 72 hours after surgery and at discharge，and Modified Rankin Scale（mRS） score at 90 days were compared between the two groups. Results The average ICP in the experimental group was lower at 7 days post-operation（12.76±2.45 vs 14.91±4.56 mmHg，P=0.002），and the rate of reaching the ICP target within 72 hours was higher than the control group（52.4% vs 33.3%，P=0.038），with an absolute risk difference increase of 19.1%，which mean that for every 5.2 patients treated，one more patient could reach the target. The hospital stay in the experimental group was shorter than that of control group（21.93±2.51 vs 23.60±3.91 days，P=0.006）. There was no statistically significant difference in mechanical ventilation time and Barthel Index score at 72 hours post-operation（P=0.104，P=0.714），but the Barthel Index score at discharge was higher in the experimental group（35.83±21.04 vs 24.76±24.69，P=0.022）. The proportion of patients with mRS≤3（mild to moderate disability） at 90 days was higher in the experimental group（30.9% vs 14.8%），and the propor-tion of patients with mRS≥4（moderate to severe disability and death） was lower（40.5% vs 52.4%，P=0.036）. Conclusion The stepped analgesia and sedation protocol based on MMM can optimize ICP management，shorten ICU stay，and improve neurological prognosis，which provide a basis for the care of patients undergoing decompressive craniectomy for large-area cerebral infarction.