The present case series evaluated the potential benefits of a flapless approach in the regenerative treatment of residual deep intrabony defects. In each of 11 patients, one periodontal defect with an intrabony component of ≥ 3 mm was treated regeneratively using enamel matrix derivative combined with a closed surgical technique. Clinical and radiographic parameters were recorded at baseline and at 12 and 24 months postoperatively. All defects experienced favorable clinical and radiographic outcomes at the 24-month follow-up. When considering only sites located in the anterior region, all experienced complete pocket closure.