Despite the various barrier membranes proposed, one of the main challenges for guided bone regeneration (GBR) is space maintenance for large defects as well as ensure adequate blood supply. The presented feasibility case series aims to introduce an original titanium frame (TF) design, customized for each defect, as a modification of well-known principles and materials for GBR, for an enhanced and more predictable horizontal and vertical bone augmentation. Three patients with significant horizontal defects were treated with pre-trimmed TFs to create needed space, a 50%-50% mixture of autograft and bovine xenograft was placed, and then covered with collagen membrane. After 8 months of healing, the sites were reopened, the titanium screws were removed with the frame. An average of 8.0 ± 1.0mm horizontal and 3.0 ± 0.0mm vertical bone gain was achieved at the time of re-entry and implant placement surgery. Bone core biopsy was obtained during the implant placement. Histomorphometric analysis revealed that 42.8% of the sample was new vital bone, 18.8% was residual bone graft particles, and 38.4% was bone marrow like structures. After 3-4 months from implant placement, the implants were restored with provisional crowns and then finalized with zirconia screw-retained crowns. This case series suggests that GBR utilizing TFs with or without collagen membranes can be considered a suitable approach for horizontal and vertical bone augmentation. However, based on only three reported cases, the result should be carefully interpreted.