Introduction: The aim of the study was to assess the impact of collaterals on the evolution of hypodensity on non-contrast CT (NCCT) in anterior circulation stroke with reperfusion by mechanical thrombectomy (MT). Methods: We retrospectively included stroke patients with middle cerebral artery occlusion who were reperfused by MT in early and late time window. Artificial intelligence (AI)-based software was used to calculate of hypodensity volumes at baseline NCCT (V1) and at follow-up NCCT 24 h after MT (V2), along with the difference between the two volumes (V2-V1) and the follow-up (V2)/baseline (V1) volume ratio (V2/V1). The same software was used to classify collateral status by using a 4-point scale where the score of zero indicated no collaterals and the score of three represented contrast filling of all collaterals. The volumetric values were correlated with the collateral scores. Results: Collateral scores had significant negative correlation with V1 (p = 0.035), V2, V2− V1 and V2/V1 (p < 0.001). In cases with collateral score = 3, V2 was significantly smaller or absent compared to V1; in those with collateral score 2, V2 was slightly larger than V1, and in those with scores 1 and 0 V2 was significantly larger than V1. These relationships were observed in both early and late time windows. Conclusions: The collateral status determined the evolution of the baseline hypodensity on NCCT in patients with anterior circulation stroke who had MT reperfusion. Damage can be stable or reversible in patients with good collaterals while in those with poor collaterals tissues that initially appear normal will frequently appear as necrotic after 24 h. With good collaterals, it is stable or can be reversible while with poor collaterals, normal looking tissue frequently appears as necrotic in follow-up exam. Hence, acute hypodensity represents different states of the ischemic brain parenchyma.