Purpose: The objective of this paper was to compare histologically and histomorphometrically a hydroxyapatite originated by algae (Algipore) versus demineralized bovine bone (Bio-Oss Geistlich Pharma, Wolhusen, Switzerland) utilised as bone substitutes in maxillary sinus floor elevation with a split-mouth design. Materials and Methods: Five healthy patients underwent a bilateral maxillary sinus floor elevation procedure under local anesthesia. In each case, residual posterior maxillary bone height was between 2 mm and 5 mm. The original bone was augmented with a split-mouth design with 100% Algipore on the test side and 100% Bio-Oss on the contralateral control side. After a healing period of 6-8 months during the re-opening surgery biopsies were retrieved and Xive Implants (Dentsply Implants, Mannheim, Germany) were placed. Results: At microscopic level both Bio-Oss and Algipore blocks resulted well osseointegrated, without inflammatory infiltrate, with an high level of mineralization, without gap between the bone and biomaterial interfaces that resulted indistinguishable. A close contact between the two faces was observed without the presence of slits. Histomorphometrical analysis showed that, on average, the percentage of medullary space was higher for the Bio-Oss compared with Algipore (38.61% ±8.90% vs. 29.23% ±7.89%). In contrast, the mean value of residual particles of biomaterials was higher in Algipore than in Bio-Oss specimens (42.86% ±18.61% vs. 22.30% ±6.40% respectively). Conclusions: The data confirmed that sinus lift carried out with Algipore performed in a similar way of that carried out with Bio-Oss and that this material is safe, predictable and without invasiveness.