Autogenous bone harvesting is a well-documented surgical procedure. Autogenous mandibular bone harvesting carries a risk of anatomical structural damage because the surgeon has no three-dimensional (3D) control of the osteotomy planes. The aim of this case series was to describe the results of mandibular bone block harvesting applying computer-guided surgery. A sample of 13 partially dentate patients presenting bone deficiencies in the horizontal and/or vertical plane were selected for autogenous mandibular bone block graft. The bone block dimension was planned through a computer-aided design (CAD) process, defining ideal bone osteotomy planes to avoid damage to anatomical structures (nerves, teeth roots, etc) and to generate a surgical guide that imposed the 3D working direction to the bone-cutting instrument. The bone block dimension was always related to the defect dimension to be compensated. A total of 13 mandibular bone blocks were harvested to treat 16 alveolar defects (9 vertical and 7 horizontal). The mean planned mesiodistal dimension of the bone block was 24.8 ± 7.3 mm, the mean height was 8 ± 1 mm, and the mean thickness was 4 ± 2 mm. None of the treated patients experienced neurologic alteration of their alveolar nerve function. The preliminary data from this case series suggested that computer-guided bone harvesting could be a concrete opportunity for clinicians to obtain an appropriate volume of autogenous bone in a safe manner.