The purpose of this study was to evaluate whether an adequate prosthetic mesh fixation in laparoscopic preperitoneal inguinal hernia repair can be achieved with fibrin sealant (FS) (Tisseel trade mark, Hyland/Immuno Div., Baxter Healthcare Corp., Deerfield, IL, USA), and compare it with stapled fixation. The use of staples for prosthetic mesh fixation in laparoscopic preperitoneal hernia repair is associated with a small but significant number of complications, mainly nerve injury and hematomas. An alternative method of fixation should be as efficient as staples in preventing graft migration. An experimental study was conducted using swine models to compare the efficacy of polypropylene mesh fixation with FS to that achieved with staples and to non-fixed mesh grafts in the preperitoneal groin area. Twenty-five female pigs were used in the study. In each pig, a prosthetic mesh was placed laparoscopically in the groin area bilaterally and fixed with either FS, staples, or left without fixation. The pigs were killed after 12 days. The following outcome measures were evaluated: macroscopic findings including graft alignment and motion, tensile strength between the grafts and surrounding tissues, and histologic findings (fibrous reaction and inflammatory response). The procedures were completed laparoscopically in 49 sites. FS was used to fix 18 grafts; 16 with staples, and 15 were not fixed. No significant difference was noted in graft motion between the FS and staple groups. The non-fixed grafts had a median motion of 5 mm (range: 0 to 10 mm), significantly more than the FS fixed (p<0.01) and stapled grafts (p<0.001). No significant difference was noted in median tensile strength between the FS and staples groups (0.955 Kg vs. 1.03 Kg, respectively) compared with 0.46 Kg in the non-fixed group (p<0.01). FS triggered a significantly stronger fibrous reaction and inflammatory response than those observed in the staples and control groups. An adequate mesh fixation in the extraperitoneal inguinal area can be accomplished using FS, based on our experimental evidence. The FS is equivalent to fixation achieved by staples and superior to no fixation. Soft fixation with FS prevents graft migration and avoids complications associated with use of staples.