Symptomatic isolated carotid artery occlusions (ICAO) can lead to disability, recurrent stroke, and mortality, but natural history and best therapeutic management remain poorly known. The objective of this study was to describe our cohort of ICAO patients with an initial medical management.We conducted a retrospective study including consecutive patients admitted to our Comprehensive Stroke Center for ICAO within 24 h after stroke onset between January 2016 and September 2018. Patients with immediate endovascular therapy (EVT) were excluded. Medical treatment was based on anticoagulation (delayed by 24 h if intravenous thrombolysis was performed). 'Rescue' EVT was considered if first-week neurological deterioration (FWND) occurred.Fifty-six patients were included, with a median National Institutes of Health Stroke Scale (NIHSS) of 3. Eleven patients (20%) had FWND during the first week, four benefited from rescue EVT. A mismatch volume > 40 cc on initial perfusion imaging and FLAIR vascular hyperintensities were associated with FWND (p = 0.007 and p = 0.009, respectively). Thirty-eight patients (69%) had a good outcome (modified Rankin Scale mRS 0-2) at 3 months, 36 (69%) had an excellent outcome (mRS 0-1). Seventeen patients (38%) had carotid patency on 3-month control imaging. Recurrences occurred in six (13%) of the survivors (mean follow-up: 13.6 months).Our results suggest that the prognosis of patients with acute ICAO was favorable with a medical strategy, albeit a substantial rate of FWND and recurrence. FWND was well predicted by a core-perfusion mismatch volume > 40 cc. Randomized controlled trials are necessary to assess the benefit of EVT in ICAO.