Thrombus on implants is dangerous, necessitating anticoagulant coatings for most of blood-contacting devices with various substances. So far, there is no universal strategy of the pertinent surface modification for different substrates, which significantly hinders the efficient research and development of blood-contacting medical devices. Herein, we propose a modular strategy to construct anticoagulant coatings on substrates including polymers, metals and nonmetallic inorganics. Inspired by the principle of primary antibody and secondary antibody in biological immunoassay, we develop a universal two-module modification approach: firstly surface activation of various substrates to generate charged surfaces with specific reactive functional groups, and secondly linking the anticoagulating moieties to the substrate via the functional groups. The feasibility of surface activation like linking the primary antibody is confirmed using 12 substrates; the final coatings analogous to linking the secondary antibody are demonstrated using a biopassive coating with 2-methacryloyloxyethyl phosphorylcholine polymer and a bioactive coating with heparin. The anticoagulant efficacy of the biopassive coating is accessed in extracorporeal circulation devices, and that of the bioactive coating in cerebral embolic protection devices minimally invasively implanted into heart through catheter. Both coatings prepared with our modular strategy have been verified in vitro and in large animals (sheep or pig).