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Introduction Current endovascular treatment (EVT) techniques failed to prove their efficacy in Medium Vessel Occlusions (MeVOs) in recent trials. Intra-arterial administration of alteplase has been proposed as a promising strategy in MT of MEVOs.Aim of Study To explore the potential advantage of Stent-retriever Assisted Intra-arterial Lysis (SAIL) in EVT of MEVOs.Method Two different compositions (fibrin:erythrocytes) of ovine clot were synthesized: erythrocyte-rich(1:1) and fibrin-rich (9:1) and embolized in an in vitro 3D-printed model simulating M2-MCA branches. The model was integrated into a closed flow-loop with circulating plasma. Thirty clots were randomized to 7:30 minutes of circulating: plasma, plasma+alteplase or plasma+alteplase using SAIL. Each study arm included 15 erythrocyte-rich clots and 15 fibrin-rich clots. Thrombolytic efficacy was assessed as the percentage of clot weight loss.Results Baseline weight of clots was similar in the 3 arms. Clot weight reduction was higher with erythrocyte-rich (39%) than with fibrin-rich clots (35%; p=0.24). Overall, as compared to the weight reduction observed with plasma (27%), weight reduction was higher with Alteplase (38%; p<0.001) and with SAIL (52%; p<0.001). SAIL was most effective reducing clot-weight in both: erythrocyte-rich (plasma 29%, alteplase 36%, SAIL 58%; p<0.001) and fibrin-rich clots (plasma 22%, alteplase 38%, SAIL 51%; p<0.001).Conclusion The SAIL technique seems to increase the fibrinolytic effect of intra-arterial administration of Alteplase and may be an effective technique to use in the EVT of MeVOs.Conflict of Interest No