Purpose: Different graft materials have been proposed to minimize the collapse of alveolar bone after tooth extraction. The aim of this study was to examine the use of porcine bone graft in fresh sockets via histomorphometric and in vivo gene expression profiling. Materials and Methods: Thirty fresh extraction sockets with three bone walls in 15 patients were selected. A split-mouth design was employed. On one side of the arch, 15 sockets received corticocancellous porcine bone as a graft, and on the other side, 15 sockets were left unfilled and considered as controls. Four months after surgery, four biopsy specimens were taken from each patient (two from the grafted site and two from the control site). The specimens were analyzed by histomorphometry and ex vivo osteoblast expansion, followed by highly sensitive osteoblast-specific gene expression profiling for Runx2, osteopontin, osteoprotegerin, type I collagen, and alkaline phosphatase by quantitative real-time reverse-transcriptase polymerase chain reaction. Comparisons were made using the Student t test. Results: After healing without complications, the grafted sites showed statistically significantly higher mean vital bone and lower mean connective tissue values than the control sites. Statistically significant higher expression of alkaline phosphatase and the matrix formation markers type I collagen and osteopontin were observed in the grafted group compared to the control group, whereas Runx2 and osteoprotegerin expression was comparable. Conclusions: Within the limits of this study, histologic examination and biomolecular evaluation confirmed good biocompatibility and high osteoconductivity of xenogeneic porcine bone in alveolar bone grafting. Keywords: alveolar ridge preservation, molecular biology, porcine bone, tooth extraction