Purpose <p>Hyperdense middle cerebral artery sign (HMCAS) is a phenomenon highly specific for acute ischaemic stroke (AIS) that can be found in brain non-contrast computed tomography (NCCT). Previous studies concerning its association with outcomes of patients undergoing mechanical thrombectomy (MT) are inconclusive. Our aim was to assess the relationship between HMCAS presence and long-term outcomes of AIS patients undergoing MT.</p> Methods <p>The study included anterior circulation AIS patients treated with MT in the University Hospital in [ANONYMIZED] from 2019 to 2021, in whom admission NCCT and one-year follow-up were available. The clinical, laboratory and imaging data, as well as following outcomes: the occurrence of successful recanalization [defined as modified treatment in cerebral infarction (mTICI) score 2b-3], haemorrhagic complications (ICH), 90-day and 365-day rates of mortality and good functional outcome [defined as modified Rankin Scale (mRS) score 0–2] were compared between groups of patients with and without HMCAS on initial NCCT. The association of HMCAS presence with the abovementioned outcomes was assessed using multivariate logistic regression analysis.</p> Results <p>Among 359 MT-treated patients with anterior circulation AIS, HMCAS was found in 244 (67.97%). The presence of HMCAS was independently associated with good functional outcome at 365 days (OR 1.956, 95% CI = 1.152–3.317, <i>p</i> = 0.013) as well as lower 90-day and 365-day mortality (OR = 0.464, 95% CI = 0.2517–0.856; <i>p</i> = 0.014 and OR 0.543, 95% CI: 0.313–0.940, <i>p</i> = 0.029, respectively).</p> Conclusion <p>The presence HMCAS on admission NCCT is associated with favourable long-term outcome in AIS patients undergoing MT.</p>