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Introduction Unlike tandem occlusions, isolated cervical internal carotid artery(cICA) was excluded from landmark trials, leaving management undefined. Whether endovascular outcomes are comparable to guideline-supported TO and whether etiology modifies this remains unknown. This study evaluated the endovascular outcomes for isolated cICA against TO and examine the role of etiology within the isolated cICA cohort.Methods We performed a retrospective analysis of a prospectively maintained thrombectomy database at a single comprehensive stroke center, including consecutive patients treated between 2010-2024. Patients with intracranial atherosclerosis were excluded. The primary analysis compared baseline characteristics and outcomes between isolated cICA and TO (ICA-Terminus/MCA-M1/MCA-M2) cohorts. A pre-specified sub-analysis within the isolated cICA cohort compared extracranial atherosclerotic vs. non-atherosclerotic etiologies. Categorical variables were compared using chi-square and continuous variables using t-test or Kruskal-Wallis test. The primary outcomes were 90-day functional independence (mRS 0-2) and mortality; secondary outcomes were parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH). Logistic regression models were adjusted for age, diabetes mellitus, atrial fibrillation, smoking, NIHSS, ASPECTS, thrombolytic administration, baseline TICI, cervical stenting, and prior stroke.Results Of 3,701 patients, 109 had isolated cICA and 232 had TO. Tandem patients presented with higher NIHSS [17 (14-22) vs 15 (10-19); p<0.01] and lower ASPECTS [8 (6-9) vs 9 (8-10); p<0.01]. Cervical stenting was performed significantly more often in isolated cICA patients (59.6% vs 12.5%; p<0.01), reflecting the predominance of extracranial atherosclerotic disease in this cohort (63.3%). Despite these differences, successful reperfusion (TICI 2b-3) was achieved at comparable rates (96.3% vs 95.3%), and adjusted 90-day functional independence, mortality, PH, and sICH were comparable between groups (all p>0.5). Within the isolated cICA cohort, 69 were atherosclerotic and 40 were non-atherosclerotic. Atherosclerotic patients were older [67 (61-73) vs 58.5 (47.5-75.5); p=0.01], more frequently smokers (46.4% vs 17.5%; p<0.01), and presented with lower NIHSS [13 (8.5-18) vs 17 (14.75-20); p<0.01]. Cervical stenting was more common in the atherosclerotic subgroup (71.0% vs 40.0%; p<0.01). Despite these baseline differences, adjusted 90-day functional independence, mortality, PH, and sICH remained comparable between etiologic subgroups (all p>0.08), though a trend toward higher hemorrhagic rates in the non-atherosclerotic group warrants attention (sICH 12.5% vs 1.4%; p=0.045 on unadjusted analysis).Conclusion Isolated cICA occlusion yields comparable reperfusion and 90-day outcomes to tandem occlusions regardless of etiology. These findings support prospective randomized evaluation of endovascular treatment in this population.Disclosures T. Yelam: None. J. Grossberg: None. S. Batista: None. R. Nogueira: None. P. Martins: None. D. Haussen: None. J. Dolia: None.Abstract E-081 Table 2Basolne cheracteristies betweon extracranial athoroscioresis and non atherosclerosisin isolated ciCA cohort