<b><i>Introduction:</i></b> The current guidelines advocate the implementation of stroke networks to organize endovascular treatment (ET) for patients with acute ischemic stroke due to large vessel occlusion (LVO) after transfer from a Primary Stroke Centre (PSC) to a Comprehensive Stroke Centre (CSC). In France and in many other countries around the world, these transfers are carried out by a physician-led mobile medical team. However, with the recent broadening of ET indications, their availability is becoming more and more critical. Here, we retrospectively analysed data of patients transferred from a PSC to a CSC for potential ET to identify predictive factors of major complications (MC) at departure and during transport that absolutely require the presence of a physician during interhospital transfer. <b><i>Methods:</i></b> This observational, single-centre study included patients with evidence of intracranial LVO transferred for ET from Perpignan to a 156 km-distant CSC between January 1, 2015 and ­December 31, 2018. We compared 2 groups: MC group (patients who required emergency intervention by the medical team due to life-threatening complications, including need of mechanical ventilation at departure) and non-MC group (all other patients who experienced no or only minor complications that could be managed by the emergency paramedics alone). <b><i>Results:</i></b> Among the 253 patients who were transferred to the CSC, 185 (73.1%) had no complication, 57 (22.6%) minor complications, and 11 (4.3%) had MC. In multivariate analysis, MC was associated with basilar artery (BA) occlusion (<i>p</i> &#x3c; 0.0001), initial National Institute of Health Stroke Scale (NIHSS) score &#x3e;22 (<i>p</i> &#x3c; 0.005), and history of atrial fibrillation (<i>p</i> &#x3c; 0.04). Among the 168 patients treated with intravenous thrombolysis (IVT), only 1 patient (0.6%) had MC due to an IVT-related adverse event during transfer. <b><i>Conclusions:</i></b> Physician-led inter-hospital transports are warranted for patients with BA occlusion, initial NIHSS score &#x3e;22, or history of atrial fibrillation. For the other patients, transfer without a physician may be considered, even if treated with IVT.