Background <p>Although landmark trials showed favorable outcomes with endovascular therapy (EVT) for large ischemic stroke, imaging protocols for patient inclusion varied. This study aims to explore the interaction between computed tomography angiography (CTA) imaging characteristics and the association of EVT with outcomes in real-world clinical practice.</p> Methods <p>This was a subanalysis of a prospective cohort study that enrolled patients with large vessel occlusion and ASPECTS 0–5 from 38 stroke centers across China between November 2021 and February 2023. Based on admission CTA imaging, the occlusion site, Tan score, cortical vein opacification score (COVES), internal cerebral veins (ICV), and clot burden score were assessed. The primary outcome was the 90-day modified Rankin Scale (mRS). Treatment effects across subgroups based on CTA imaging characteristics were analyzed using ordinal regression analysis, and interaction analysis was performed to assess whether these characteristics modified the effect of EVT on 90-day mRS.</p> Results <p>Among the 460 patients (255 male, 55.4%), the EVT group was younger than SMT group (67 years [IQR, 58–77] vs. 72 years [IQR, 65–79]). COVES and Tan score significantly modified the association between EVT and 90-day mRS (<i>P</i> &lt; 0.001 and <i>P</i> = 0.023 for interaction, respectively), with a larger effect size observed in patients with COVES 3–6 (adjusted common odds ratio [acOR], 2.43 [95% CI, 1.39–4.27]; <i>P</i> = 0.002) and Tan score 2–3 (acOR, 2.78 [95% CI, 1.24–6.24]; <i>P</i> = 0.013). In contrast, occlusion site, ICV score, and clot burden score did not modify the effect of EVT.</p> Conclusion <p>Better arterial and venous collaterals in patients with large ischemic stroke are associated with favorable outcomes and may modify the effect of EVT. This analysis provides preliminary evidence supporting the role of baseline CTA imaging in guiding EVT selection for these patients.</p>