Laparoscopic ventral hernia repair requires an intraperitoneal prosthetic; however, these materials are not without consequences. We evaluated host reaction to intraperitoneal placement of various prosthetics and the functional outcomes in an animal model. Mesh (n = 15 per mesh type) was implanted on intact peritoneum in New Zealand white rabbits. The mesh types included ePTFE (DualMesh), ePTFE and polypropylene (Composix), polypropylene and oxidized regenerated cellulose (Proceed), and polypropylene (Marlex). Adhesion formation was evaluated at 1, 4, 8, and 16 weeks using 2-mm mini-laparoscopy. Adhesion area, adhesion tenacity, prosthetic shrinkage, and compliance were evaluated after mesh explantation at 16 weeks. DualMesh had significantly less adhesions than Proceed, Composix, or Marlex at 1, 4, 8, and 16 weeks (P < 0.0001). Marlex had significantly more adhesions than other meshes at each time point (P < 0.0001). There were no statistically significant differences in adhesions between Proceed and Composix meshes. After mesh explantation, the mean area of adhesions for Proceed (4.6%) was less than for Marlex (21.7%; P = 0.001). The adhesions to Marlex were statistically more tenacious than the DualMesh and Composix groups. Overall prosthetic shrinkage was statistically greater for DualMesh (34.7%) than for the remaining mesh types (P < 0.01). Mesh compliance was similar between the groups. Prosthetic materials demonstrate a wide variety of characteristics when placed inside the abdomen. Marlex formed more adhesions with greater tenacity than the other mesh types. DualMesh resulted in minimal adhesions, but it shrank more than the other mesh types. Each prosthetic generates a varied host reaction. Better understanding of these reactions can allow a suitable prosthetic to be chosen for a given patient in clinical practice.