Glucosamine‐ and N‐acetyl glucosamine‐containing polymers are being used in an increasing number of biomedical applications, including in products for surface (topical) hemostasis. The studies presented here investigate the relationship between the structure (conformation) and function (activation of hemostasis) of glucosamine‐based materials. Several polymer systems were studied, including fibers isolated from a microalgal source containing poly‐N‐acetyl glucosamine polymers that are organized in a parallel, hydrogen‐bonded tertiary structure and can be chemically modified to an antiparallel orientation; and gel formulation derivatives of the microalgal fibers consisting of partially deacetylated (F2 gel) and fully deacetylated (F3 gel) polymers. Comparison of the properties of the poly‐N‐acetyl glucosamine fiber‐derived materials with chitin, chitosan, and commercial chitosan‐based products are presented. Several studies were performed with the glucosamine‐based materials, including (1) an analysis of the ability of materials to activate platelets and turnover of the intrinsic coagulation cascade, (2) an examination of the viscoelastic properties of mixtures of platelet‐rich plasma and the glucosamine‐based materials via thromboelastography, and (3) scanning electron microscopic studies to examine the morphology of the glucosamine‐based materials. The results presented demonstrate that hemostatic responses to the glucosamine‐based materials studied are highly dependent on their chemical nature and tertiary/quaternary structure. The unique natural microalgal fibers were found to have strongly prohemostatic activity compared to the other materials studied. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007