Purpose: This study aims to assess the differences between a leukocyte- and platelet-rich fibrin (L-PRF) and deproteinized bovine bone mineral block and a combination of 50% autogenous bone (AB) and 50% deproteinized bovine bone mineral (DBBM) as grafting material for horizontal guided bone regeneration (GBR). Materials and Methods: This randomized double-blind split-mouth clinical trial included 13 subjects requiring bilateral horizontal bone augmentation. Each patient received both treatment modalities: one side of the jaw was treated by GBR with the L-PRF and deproteinized bovine bone mineral block, and the other side with a 50/50 mixture of AB and DBBM. Cone beam computed tomography (CBCT) scans were used to evaluate horizontal bone width (HBW) and buccal bone thickness (BBT) at various time points: baseline (T0), immediately post-augmentation (T1), at implant placement (T2), and one year after abutment connection (T4). Bone sounding (BS) was also used to verify CBCT measurements. Results: No statistically significant differences were found in HBW gain between test (L-PRF) and control (AB/DBBM) sites at any timepoint. Both sites showed significant HBW loss post-implant placement, with more bone volume lost at higher crestal levels (Sh0 > Sh2 > Sh4). At the Sh2 level, 48.8% of the HBW gain at T1 was lost by T4 in test sites, and 46.2% in control sites. Similarly, BBT at Sh2 reduced from 4.7 ± 1.0 mm to 1.3 ± 1.5 mm in test sites and from 2.1 ± 1.0 mm to 0.9 ± 0.8 mm in control sites. Both groups of sites had one complication, resulting in a 91.6% success rate for both treatments. The cumulative survival rate of implants was 100% at 16 months, with a mean interproximal bone level (IBL) loss of 0.2 ± 0.9 mm and 0.1 ± 0.6 mm for test and control sites, respectively. Conclusions: No statistically significant differences were found between the AB/DBBM composite graft and the L-PRF and bovine bone mineral block for horizontal GBR. Significant resorption of grafted volume occurs within 25 months, continuing post-implant placement. Further research with larger sample sizes is needed to confirm these findings and optimize GBR techniques.