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Purpose The increased demand for training of mechanical thrombectomy in ischemic stroke and development of new recanalization devices urges the creation of new simulation models both for training and device assessment. Clots properties have shown to play a role in procedural planning and thrombectomy device effectiveness. In this study, we analyzed the characteristics and applicability of completely synthetic, animal-free clots in the setting of an in-vitro model of mechanical thrombectomy for training and device assessment. Methods Synthetic clots based on agarose (n = 12) and silicone (n = 11) were evaluated in an in-vitro neurointervention simulation of mechanical thrombectomy with clot extraction devices. Calcified clots of mixed nature were simulated with addition of 3D printed structures. 9 clots were excluded due to insufficient vessel occlusion and failure to integrate with clot extraction device. Synthetic thrombi were characterized and compared using a categorical score-system on vessel occlusion, elasticity, fragmentation, adherence and device integration. Results Both agarose-based and silicone-based clots demonstrated relevant flow arrest and a good integration with the clot extraction device. Silicone-based clots scored higher on adherence to the vessel wall and elasticity. Conclusion Selected synthetic clots can successfully be implemented in an in-vitro training environment of mechanical thrombectomy. The clots’ different properties might serve to mimic fibrin-rich and red blood cell-rich human thrombi.