Background: Telemedicine is improving acute stroke care in remote areas. Delay in hospital-to-hospital transfer is a common reason why acute ischemic stroke patients are excluded from interventional therapy. The progressive implementation of these procedures, requiring highly specialized professionals in comprehensive stroke centers, will certainly challenge even more the geographic equity in the access to the best acute stroke treatments. We aimed to assess the benefits of telemedicine in selecting stroke patients for endovascular treatments. Methods: In our Reference Comprehensive Stroke Center (RCSC), we perform urgent intra-arterial procedures in acute stroke patients. Patients may be primarily admitted (PA) or referred from community hospitals with (TMHs; 2 centers) or without telemedicine (nonTMHs; 7 centers). We prospectively studied all consecutive stroke patients undergoing urgent endovascular recanalization procedures in the RCSC. We studied different outcome measures according to the patients' initial admission: PA patients, TMH patients or nonTMH patients. For all patients, demographic and outcome data including serial National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores at 3 months were recorded. Clinical improvement was defined as a decrease ≥4 points on the NIHSS at 7 days or discharge and favorable outcome as mRS ≤2 at 3 months. Whether an endovascular procedure was indicated was decided according to clinical, radiological and transcranial Doppler (TCD) data, independently of the patient's initial admission center. Results: During a 2-year period, 119 patients received endovascular treatment: PA patients 74 (63.1%), TMH patients 25 (20.5%), nonTM patients 20 (16.4%). The mean distance to the RCSC was 52 ± 15 km for TMHs and 34.5 ± 12 km for nonTMHs (p = 0.4). There were no differences in baseline characteristics including age (71, 71.6 and 66.5 years; p = 0.25), baseline NIHSS (18.5, 19 and 18; p = 0.57) and previous use of intravenous tissue plasminogen activator (56.5, 56.5 and 57.9%; p = 0.95). The rate of recanalization (modified Thrombolysis in Cerebral Infarction Score ≥2a) was similar in all groups (75, 66.6 and 68.4%; p = 0.682). TMH and PA patients had similar clinical improvement (61 vs. 63.8%; p = 0.51) and good functional outcome (36.8 vs. 35.3%; p = 0.722). Conversely, nonTMH patients presented a lesser degree of clinical improvement (31.3%) and poorer functional outcome (15.8%) than TMH (p = 0.019 and p = 0.046) and PA patients (p = 0.05 and p = 0.013). TMH patients had significantly shorter door-to-groin puncture times (47 vs. 69 min; p = 0.047). Conclusions: Telemedicine assessment to select patients for endovascular procedures improves the efficiency in stroke management and possibly the early and long-term outcome in patients receiving intra-arterial reperfusion treatment.