A lack of bone volume may compromise a correct three-dimensional implant placement. This study was designed to evaluate the clinical and radiographic outcomes of simultaneous horizontal guided bone regeneration (GBR) performed using autogenous bone or blood-derived products mixed with a bone xenograft. The study population consisted of patients operated on using one of two clinical protocols for GBR: group A, which used autogenous bone mixed with a bone xenograft, and group B, which used advanced platelet-rich fibrin (A-PRF) mixed with a bone xenograft. The primary outcome was the clinical gain in the peri-implant defect. The secondary outcomes included an analysis of the postoperative healing, periodontal parameters, marginal bone loss, and occurrence of adverse events. All of the surgeries were carried out successfully. One patient in each group experienced a case of early implant loss, and three patients (one in group A and two in group B) presented biologic complications. The mean peri-implant vertical defect heights at baseline in group A and group B were 3.6 ± 0.9 mm and 4 ± 1.5 mm, respectively (P = .382). No statistically significant differences in the mean residual defect heights (P = .521) or in the postoperative wound healing (P = .611) were observed. Stable peri-implant marginal bone levels were recorded after loading in both groups. The use of A-PRF combined with a particulate bone xenograft and covered with a fixed collagen membrane may provide clinical results similar to those obtained via autogenous bone mixed with bone xenograft.