Introduction: Endovascular therapy (EVT) improves clinical outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Transfer from a referring hospital (RH) to a comprehensive stroke center (CSC) renders some patients ineligible for EVT due to infarct expansion. We evaluated the association of clinical and imaging factors, and the effect of time on infarct expansion using CT ASPECTS decay, subsequent impact on thrombectomy decision and consequent clinical outcomes. Methods: We retrospectively analyzed data on patients with AIS from LVO transferred for potential EVT from a RH to our comprehensive stroke center (hub) between September 2015 and December 2017. Patients were stratified into two groups, CT decay vs. CT non-decay, where CT ASPECTS decay was defined as deterioration of score from ≥6 at RH to <6 at hub (since AHA guidelines for EVT are ASPECTS > 6). Baseline characteristics, clinical and imaging variables were assessed for association with decay. Good outcomes (90 day mRS 0-2) were compared between the two groups. Multivariable logistic regression was applied to identify the independent predictors for decay and the adjusted odds ratio (aOR) was calculated. Results: Of a total 154 patients, 32 (21%) had ASPECTS decay. Baseline characteristics were similar in both groups except patients with decay had higher NIHSS [Median (IQR), 21(16, 25) vs. 16 (11, 21); P <. 001] and poor collateral scores (mTICI 0-1) [n (%) 17 (68) vs. 22 (29); P 0.003]. Of the 101 patients that did not undergo EVT on arrival to hub, 26 were due to decay in ASPECTS, 20 due to absence of LVO and 19 due to clinical improvement. Transfer time was similar in patients with decay vs. non-decay [Median (IQR), minutes, 164 (124.5, 198.5) vs. 155.5 (117, 191); P 0.64]. Higher initial NIHSS [aOR 1.12 (95% CI: 1.03, 1.23); P 0.009] and poor collateral score [aOR 4.65 (95% CI: 1.65, 13.07); P 0.004] were associated with decay. None of the patients with decay had a good outcome [n (%), 0 (0) vs.41 (41); P <0.0001]. Conclusion: In patients transferred for potential EVT, severity of stroke at initial presentation and poor collateral circulation had significant impact on ASPECTS deterioration. This information can be employed to develop stroke systems of care to triage patients with LVO to a CSC