The application value of mechanical thrombectomy (MT) in acute large-vessel occlusion cerebral infarction has been confirmed, but considering the poor prognosis of large-core infarction (LCI), the current guidelines and practices are based on anterior circulation small-core infarction. Reducing the perioperative complications of thrombectomy in LCIs is the key to saving more patients previously considered unsuitable for thrombectomy. Patients with acute anterior circulation cerebral infarction who were admitted to Suining Central Hospital of Sichuan Province from January 2022 to December 2023 and whose Alberta Stroke Program Early Computed Tomography Score value was 3–5 (the score range was 0–10, and the lower the score was, the larger the infarct area) or whose infarct core volume was ≥70 mL and who received MT were enrolled consecutively. The patients were grouped based on whether they were treated with mild hypothermia (mild hypothermia treatment group vs. conventional treatment group). Patients who were evaluated preoperatively for large-core cerebral infarction and underwent mild hypothermia treatment were performed immediately after MT. The clinical data of the patients were collected. The primary outcome events were the incidence of cerebral hernia within one week after the operation and the rate of requiring decompressive craniectomy (%). The secondary outcome was the modified Rankin scale (mRS) score at 90 days (the score range was 0–6, and the higher the score was, the greater the degree of functional disability). A total of 64 patients were included. Twenty-nine patients were assigned to the mild hypothermia treatment group, and 35 patients were assigned to the conventional treatment group. There was no significant difference in the baseline data between the two groups. The proportions of cerebral hernia and the need for decompressive craniectomy within one week after the operation were significantly lower in the mild hypothermia treatment group than in the conventional treatment group (31% vs. 57.1%, odds ratio [OR] 0.338, 95% confidence interval [CI] 0.120–0.948; p = 0.037). The proportion of patients who underwent decompressive craniectomy in the mild hypothermia treatment group was significantly lower (13.8% vs. 42.8%, OR 0.213, 95% CI 0.061–0.745, p = 0.011). There was no significant difference in the mRS score between the two groups at 90 days (4.31 ± 1.75 vs. 4.48 ± 1.57, p = 0.456) or in the proportion of patients with a good prognosis (mRS 0–3) between the two groups (OR 0.569, 95% CI 0.18–1.793, p = 0.333). Mild hypothermia treatment can reduce the incidence of early cerebral hernia and the need for decompressive craniectomy in patients with acute large-core cerebral infarction after MT; this treatment can be used as an important adjuvant treatment after thrombectomy for LCI, but may not change the long-term prognosis.