Background: The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. Objective: Evaluate the potential of DNA reacting surface to aid the retention of the main clot as well as of its small fragments within the thrombectomy device and improve the potential of MT procedures. Methods: Device-suitable alloy experimental samples were coated with 15 different compounds and contacted with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus flowing blood elements, in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests aiming to studying clot retrieval and distal emboli release, concomitant with contact aspiration, using an M1 occlusion model. Results: Binding properties of samples coated with all compounds were increased for DNA (c.ca 3-fold) and decreased (c.ca 5-fold) for blood elements, essentially platelet, as compared to the bare alloy samples, in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced secondary embolism during experimental recanalization of occluded artery 3D model by thrombectomy procedures. Conclusion: Our results suggest that device coating with DNA-binding compounds can considerably improve the outcome of MT procedures in stroke patients.