This two-center human clinical trial evaluated recombinant human bone morphogenetic protein-2 delivered in an absorbable collagen sponge (rhBMP-2/ACS) for either alveolar ridge preservation after tooth extraction or augmentation of localized osseous defects. This 24-month study comprised two parts: a 4-month acute safety and bone induction period (Part I) followed by a 20-month, osseointegration, functional restoration, and long-term safety evaluation (Part II). The primary objective of Part I, discussed in this article, was to evaluate the short-term safety and technical feasibility of the rhBMP-2 device implantation. Twelve patients (six preservation and six augmentation) were enrolled in the investigation. Patient safety was monitored by oral examinations, radiographs, and the collection of blood samples to measure serum chemistries, hematology, and potential antibody formation. Technical feasibility was evaluated by collecting information relating to the handling properties of the rhBMP-2/ACS device. The ability of various evaluative tools to measure the bone-inducing activity of the rhBMP-2/ACS device was also assessed. The clinical results suggested that rhBMP-2/ACS was well tolerated locally and systemically, with no serious adverse events. The device was found to be easily handled and adapted to the ridge and extraction socket. Using direct measurements, all sites demonstrated firmness and fullness to palpation at 4 weeks; however, a loss of volume was noted in some treatment areas between 4 and 8 weeks. Augmentation of the alveolar ridge was not observed in the patients as assessed by the evaluation techniques. This trial indicated that the use of rhBMP-2/ACS to preserve alveolar ridge after tooth extraction or augmentation of localized defects is safe and feasible. Bone fill was observed in all alveolar sockets filled with the rhBMP-2 device.