Purpose: The histomorphometric results of sinus floor augmentation with deproteinized bovine bone (DBB) and a new fully synthetic bone substitute, poly(lactic-co-glycolic acid/hydroxyapatite) (PLGA/HA), were compared in humans. Materials and Methods: Twelve maxillary sinuses of eight patients requiring major maxillary sinus floor augmentation and free of concomitant conditions (ASA scores 1 and 2) were studied. Lateral sinus augmentation was performed using DBB or PLGA/HA grafts; sites were randomly assigned to control or test groups. Patients were reexamined approximately 6 months after grafting using cone beam computed tomography scans, and biopsy samples were harvested from implant sites. Total bone volume, residual graft material volume, and new bone volume were assessed. Results: Healing times were similar between groups. Measurable biopsy specimens were available from four of the test sites and six of the control sites. PLGA/HA grafts showed no trace of graft material, whereas DBB grafts had a mean graft area of 16.5% (P .05). Mean percent newly formed bone tended to be greater for PLGA/HA (44.45%) than for DBB (27.51%). Mean total volume percent did not differ significantly: PLGA/HA = 44.45%, DBB = 44.10%. Conclusion: DBB and PLGA/HA produced similar total bone volumes. PLGA/HA appeared to be completely resorbed, whereas DBB presented residual graft material. With the limitations due to the small sample size, both materials were suitable for sinus floor augmentation. Keywords: bone graft, histomorphometry, in vivo, PLGA, sinus elevation, tissue engineering