The purpose of this study was to investigate the effects of early adhesiolysis on long-term adhesion formation after the intraperitoneal implantation of polypropylene (PP) mesh and expanded polytetrafluoroethylene (ePTFE) mesh in a rabbit model. Through a small midline laparotomy a 2 x 2-cm piece of mesh (n = 80) was sewn to an intact peritoneum on each side of a midline incision in 40 New Zealand White rabbits. Two types of ePTFE mesh [Dual Mesh (Dual) and modified Dual Mesh (C-Type), W.L. Gore and Associates, Flagstaff, AZ] and PP mesh (Marlex, C.R. Bard, Murray Hill, NJ) were compared. In 10 rabbits (n = 20) a laparoscopic adhesiolysis (LapA) was performed at one week. Mesh adhesions were scored using a modified Diamond scale (0, 0%; 1, 1-25%; 2, 26-50%; and 3, > 50%) at 1, 3, 9, and 16 weeks by serial microlaparoscopic (2 mm) examinations. After recording the final adhesion score at 16 weeks the prosthetic biomaterials were excised en bloc with the anterior abdominal wall for histologic evaluation of mesothelial layer growth (%) on the visceral surface of the mesh. Statistical differences (P value < 0.05) were measured by chi-square and Wilcoxon signed rank tests. There were no statistical differences in mean adhesion scores at adhesiolysis at 7 days. The mean adhesion scores in the groups undergoing laparoscopic adhesiolysis was statistically less (P < 0.05) for PP and both ePTFE meshes at 3-, 9-, and 16-week intervals compared with those not undergoing adhesiolysis. The percentage of mesothelialization on the visceral surface of the mesh was not statistically different between the adhesiolysis and control groups for any of the prosthetic biomaterials. Laparoscopic adhesiolysis at one week minimizes subsequent adhesion formation to PP and ePTFE mesh over a 4-month follow-up. Adhesion formation within the first 7 days after mesh implantation appears to determine the long-term adhesion score. Eliminating adhesions to mesh by mechanical or other means during this critical time may control adhesions to the mesh and subsequent mesh-related complications.