We compared the wound-bursting strength (WBS), mode of adhesive failure and surface characteristics of two FDA-approved tissue adhesives for skin closure in an incisional rat model using a randomized, controlled, blind animal experiment. Standardized 2-cm full-thickness incisions were made in duplicate on both sides of 15 rats and closed with Indermil, or High Viscosity Dermabond (HVD) following manufacturers' instructions. WBS was measured 5 min later with a validated commercial instrument. Wound sections were also observed under light and scanning electron microscopies. Indermil was significantly weaker than HVD (mean difference, 143 mmHg; 95% CI, 42-229 mmHg, P = 0.002). The mode of failure for Indermil was primarily cohesive in the adhesive and the primary failure mode for the HVD was interfacial (chi(2), p < 0.01). Microscopic observations demonstrated that application of HVD resulted in a thick, uniform and smooth surface while Indermil resulted in a thin, irregular, cracked surface. We conclude that HVD is stronger, thicker and more uniform than Indermil.