Background: The objectives of this study are to compare differences in histologic and clinical healing following tooth extraction and ridge preservation using two different xenograft treatment protocols. Methods: Forty-four patients with a non-molar tooth that required extraction and planned implant placement were randomly allocated into two ridge preservation protocol groups. Protocol 1 used a xenograft material consisting of 90% anorganic bovine bone in combination with 10% porcine collagen fibers combined with a resorbable bilayer membrane composed of non-cross-linked porcine types I and III collagen. Protocol 2 used a xenograft sponge composed of 70% cross-linked type I bovine collagen coated with a layer of non-sintered hydroxyapatite mineral on its surface combined with a resorbable membrane composed of type I porcine collagen cross-linked by natural ribose glycation. Following 21 weeks of healing, clinical measurements were repeated, and a core biopsy was obtained and prepared for histologic evaluation of percentages of vital bone, residual graft, and connective tissue/other (CT/other). Results: Similar percentages of CT/other were detected between protocols, with no significant difference between groups (P = 0.763). A significantly greater percentage of vital bone was detected in specimens in protocol 2 (P <0.001). Protocol 1 presented with a mean of 32.83% +/- 14.72% vital bone, 13.44% +/- 11.57% residual graft material, and 53.73% +/- 6.76% CT/other. Protocol 2 presented with a mean of 47.03% +/- 9.09% vital bone, no detectable residual graft material, and 52.97% +/- 9.09% CT/other. Clinically, no significant differences in dimensional changes were evident between ridge preservation protocols. Conclusion: To the best of our knowledge, this study represents the first randomized controlled trial to evaluate clinical and histologic differences seen when using these two xenograft protocols for ridge preservation.