<p>This research introduces carboxymethyl kappa-carrageenan-chitosan polyelectrolyte multilayers as a promising and sustainable alternative to heparin, used in surface treatments for blood-contacting medical devices. The polysaccharide-based surface coatings have good cytocompatibility and resist microbial adhesion of both Pseudomonas aeruginosa and Staphylococcus aureus. The blood compatibility of surfaces containing carboxymethyl-kappa-carrageenan was directly compared to similar polyelectrolyte multilayers containing heparin. The carboxymethyl-kappa-carrageenan surfaces inhibit whole-blood clotting like heparin-containing surfaces. Blood clotting is mediated by both protein-surface and cell-surface interactions. The carboxymethyl-kappa-carrageenan surfaces adsorb more fibrinogen and less albumin than the heparin surfaces, and they also exhibit reduced platelet and leukocyte adhesion, compared to heparin surfaces. These results suggest that carboxymethyl-kappa-carrageenan may represent a sustainable alternative to heparin as an anticoagulant surface modification.</p>