Bone defects lead to aesthetic and functional losses, causing dental rehabilitation to be more difficult. The objective of this work is to histologically assess the hard tissue healing of bone defects filled with platelet-rich fibrin (PRF) alone or as an adjuvant for mixing with and covering anorganic bovine bone (ABB), compared to ABB covered with a resorbable collagen membrane (CM). This study was designed as a crossover animal study. Four 5-mm tibia defects, 5 mm apart from each other, were surgically created on the tibias of 6 sheep. The defects were randomly filled with ABB + CM; PRF alone; ABB+PRF; or were left empty. The animals were euthanized on days 10, 20, and 40 post-operatively. No group showed any signs of bone necrosis. Inflammation was observed in 2 control and 3 test defects with no statistically significant difference between groups at each time point. The ABB + CM and ABB + PRF groups experienced the highest bone regeneration ratios. No differences between the empty-defect and PRF groups were observed in regard to bone regeneration. No statistical difference was observed between the ABB+PRF and ABB + CM groups in regard to bone regeneration and the amount of residual graft material at each time point. The use of PRF should be preferred due to its autogenous origin, low cost, and ease of use.