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Background: Malignant middle cerebral artery infarction (MMI) can cause life-threatening edema with high mortality rates. Randomized controlled trials (RCTs) have shown that decompressive hemicraniectomy (DC) can improve survival rate and functional outcome in selected MMI patients. However, real-world outcomes are less well described.

Objective: To investigate DC indications, timing, and outcomes in MMI patients treated at 4 Swedish neurosurgical centers and the degree of alignment of real-world patient selection with eligibility criteria from 2 landmark RCTs–DESTINY I & II.

Methods: This retrospective, Swedish multicenter (n = 4) cohort study included 335 MMI patients treated with DC between 2008 and 2022. Demographics, clinical and radiological status, surgical factors, and 6-month outcomes (modified Rankin Scale [mRS]) were collected and compared across centers and with DESTINY trials.

Results: Median age was 55 (48–61) years, and 75% were male. Pre-DC, median Glasgow Coma Scale Motor score was 5 (5–6) and Charlson Comorbidity Index score was 3 (3–4). DC was performed at a median of 38 (25–56) hours from stroke onset. Median mRS at 6 months was 4 (4–5), 24% had mRS ≤ 3, and mortality was 17%. Only 19% and 12% of patients would have qualified for DESTINY I and II trials, respectively.

Conclusions: Indication and timing of DC as a treatment of MMI demonstrated notable discrepancies in surgical practice across centers and compared to landmark RCTs. However, despite differences in timing and indications for DC, the outcome did not differ significantly across centers. Our findings provide insight into the outcome of DC performed for MMI outside the strict criteria supported by level 1 evidence.