This case series evaluated the healing of deep intrabony defects treated with a combination of enamel matrix derivative and autologous particulate bone harvested from the buccal and lingual/palatal cortical plate with a Piezosurgery device. A total of 15 defects with a predominantly one- or two-wall component were consecutively treated in 15 patients with advanced chronic periodontitis. In all selected sites, the three-wall component was ≤ 25% of the total defect depth. Clinical and radiographic parameters were recorded at baseline and 12 and 24 months postoperatively. All defects showed favorable clinical and radiographic outcomes at the 24-month follow-up. The probing depth reduction was 4.4 ± 1.6 mm, and more than 50% of the defects presented clinical attachment level gain of at least 5 mm. The bone fill was 3.1 ± 1.6 mm.