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Background Several grafting materials have been used in sinus augmentation procedures including autogenous bone, demineralized freeze-dried bone, hydroxyapatite, β-tricalcium phosphate, anorganic deproteinized bovine bone, and combination of these and others. Yet, the issue of the optimal graft material for sinus floor augmentation is controversial. Purpose This prospective, randomized split-mouth study was undertaken to histomorphometrically compare a biphasic calcium phosphate (BCP) alloplastic bone substitute and a human bone mineral allograft (freeze-dried bone allograft, FDBA) in patients undergoing bilateral maxillary lateral sinus floor augmentation. Material and methods Apico-coronal core biopsies were harvested at 9 months from 26 bilateral sites in 13 treated patients. Specimens were processed for histological and histomorphometrical analyses. Results Newly formed bone (NB) was evident in all specimens with values of 27.5% and 24.0% at the FDBA and BCP sites, respectively ( P = .331). The residual graft particle values were 12.5% and 25.4% ( P = .001), and the connective tissue values were 60.0% and 50.6%, respectively. The osteoconductive value was 52.6% for the FDBA and 26.7% for the alloplast ( P = .001). The values for the measured residual graft particles, connective tissue, and osteoconductivity, but not for NB, showed highly significant differences between the two groups. All sections in the alloplast material showed evidence of a light chronic inflammatory infiltrate, mainly comprising lymphocytes and multinucleated giant cells. Conclusions Both graft materials are suitable for sinus floor augmentation, with the allograft material being more osteoconductive. [ABSTRACT FROM AUTHOR]