Purpose: Augmentation of the sinus floor with autogenous bone often requires an extra donor site, which is associated with a risk of morbidity, and current grafting protocols involve healing times of up to 9 months. In this prospective in vivo study, the time-dependent efficacy of PepGen P-15 Putty, a combination of bovine hydroxyapatite and synthetic peptide in a sodium hyaluronate carrier, was evaluated in sinus grafting. Materials and Methods: Twenty-four edentulous patients received bilateral sinus augmentations with PepGen P-15 Putty, which mimics the cell-binding domain of type I collagen responsible for cell migration, differentiation, and proliferation. The patients were randomly divided into four groups of six patients each, corresponding to 2, 4, 6, and 9 months of healing postaugmentation. After these time intervals, bone biopsy specimens were retrieved through the alveolar bone crest into the augmented sinus, and subsequently oral implants were placed. The specimens were immersed in buffered formalin, scanned with a desktop microcomputed tomography machine, and processed for histologic and histomorphometric evaluation. A mixed model was used for statistical analysis. Results: Three-dimensional microcomputed tomography depicted the distinct structure of trabecular bone encompassing remnants of PepGen, and histologic evaluation revealed osteoblasts and osteoid with osteocytes in the vicinity of the PepGen particles at all healing stages. Histomorphometric results indicated an increase in the newly formed bone fraction in the specimens as follows: 21.3% (± 2.33) at 2 months, 21.9% (± 8.9) at 4 months, 28.5% (± 6.9) at 6 months, and 29.8% (± 11.8) at 9 months. The differences were statistically insignificant. All implants placed in the augmented sites integrated and were restored prosthetically. Conclusions: PepGen can be used successfully for maxillary sinus augmentation. These data provide evidence that implant placement, even after only 2 months of healing, may be possible. Keywords: bone substitute, dental implants, histology, maxillary sinus augmentation, microcomputed tomography, synthetic cell-binding peptide