The increasing economic burden of wound healing in healthcare systems requires the development of functional therapies. Xenografts with preserved extracellular matrix (ECM) structure and biofunctional components overcome major limitations of autografts and allografts (e.g. availability) and artificial biomaterials (e.g. foreign body response). Although porcine mesothelium is extensively used in clinical practice, it is under-investigated for wound healing applications. Herein, we compared the biochemical and biological properties of the only two commercially available porcine mesothelium grafts (Meso Biomatrix® and Puracol® Ultra ECM) to traditionally used wound healing grafts (Endoform¿, ovine forestomach and MatriStem®, porcine urinary bladder) and biomaterials (Promogran¿, collagen/oxidized regenerated cellulose). The Endoform¿ and the Puracol® Ultra ECM showed the highest (p<0.05) soluble collagen and elastin content. The MatriStem® had the highest (p<0.05) basic fibroblast growth factor (FGFb) content, whereas the Meso Biomatrix® had the highest (p<0.05) transforming growth factor beta-1 (TGF-ß1) and vascular endothelial growth factor (VEGF) content. All materials showed tissue-specific structure and composition. The Endoform¿ and the Meso Biomatrix® had some nuclei residual matter. All tissue grafts showed similar (p>0.05) response to enzymatic degradation, whereas the Promogran¿ was not completely degraded by matrix metalloproteinase (MMP)-8 and was completely degraded by elastase. The Promogran¿ showed the highest (p<0.05) permeability to bacterial infiltration. The Promogran¿ showed by far the lowest dermal fibroblast and THP-1 attachment and growth. All tested materials showed significantly lower (p<0.05) tumor necrosis factor-alpha (TNF-¿) expression than the lipopolysaccharides group. The MatriStem® and the Puracol® Ultra ECM promoted the highest (p<0.05) number of micro-vessel formation, whereas the Promogran¿ the lowest (p<0.05). Collectively, these data confer that porcine mesothelium has the potential to be used as a wound healing material, considering its composition, resistance to enzymatic degradation, cytocompatibility, and angiogenic potential.