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Background/objective: Space occupying cerebral edema is the most feared early complication after large ischemic stroke, occurring in up to 30% of patients with middle cerebral artery (MCA) occlusion, and is reported to peak 2-4 days after injury. Little is known about the factors and outcomes associated with peak edema timing, especially when it occurs after 96 hours. We aimed to characterize differences between patients who experienced maximum midline shift (MLS) or decompressive hemicraniectomy (DHC) in the acute (<48 hours), average (48-96 hours), and subacute (>96 hours) groups and determine whether patients with subacute peak edema timing have improved discharge dispositions., Methods: We performed a two-center, retrospective study of patients with ≥1/2 MCA territory infarct and MLS. We constructed a multivariable model to test the association of subacute peak edema and favorable discharge disposition, adjusting for age, admission Alberta Stroke Program Early CT Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS), acute thrombolytic intervention, cerebral atrophy, maximum MLS, parenchymal hemorrhagic transformation, DHC, and osmotic therapy receipt., Results: Of 321 eligible patients with MLS, 32%, 36%, and 32% experienced acute, average, and subacute peak edema. Subacute peak edema was significantly associated with higher odds of favorable discharge than non-subacute swelling, adjusting for confounders (aOR, 1.85; 95% CI, 1.05-3.31)., Conclusions: Subacute peak edema after large MCA stroke is associated with better discharge disposition compared to earlier peak edema courses. Understanding how the timing of cerebral edema affects risk of unfavorable discharge has important implications for treatment decisions and prognostication., Competing Interests: Conflicts of Interest: The Authors declares that there are no conflicts of interest. The authors confirm that manuscript complies with all instructions to authors. The authors confirm that authorship requirements have been met and the final manuscript was approved by all authors. The authors confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. The authors confirm adherence to ethical guidelines and indicate ethical approvals (IRB) and use of informed consent, as appropriate. The study was approved to be conducted by the Massachusetts General Brigham Institutional Review Board (2017P002564) and informed consent was not required. The authors prepared the report according to Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines. CJO were responsible for the project ideation, and study direction. CJO, JJS, RAS, JD, JEP were responsible for subsequent design of the study. CJO, RAS, JEP, ISYK, BB, SC, MC, SD organized and collected the patient data for analysis. JJS, RAS, JEP contributed to analysis, CJO, JJS, RAS, JEP, BB, JD, DMG, SMS, EJB assisted in interpretation. JJS, RAS, and CJO drafted the manuscript, and BB, SC, QH, SMS, EJG, EJB, and DMG contributed to critical editing and revisions. CJO is the guarantor.