Objectives: The aim of this study is to report on the treatment of mandibular Class II furcation defects with enamel matrix protein derivative (EMD) combined with a βTCP/HA (β-tricalcium phosphate/hydroxyapatite) alloplastic material. Method and Materials: Thirteen patients were selected. All patients were nonsmokers, systemically healthy, and diagnosed with chronic periodontitis; had not taken medications known to interfere with periodontal tissue health and healing; presented one Class II mandibular furcation defect with horizontal probing equal to or greater than 4 mm at buccal site. The clinical parameters evaluated were probing depth (PD), relative gingival margin position (RGMP), relative vertical clinical attachment level (RVCAL), and relative horizontal clinical attachment level (RHCAL). A paired Student t test was used to detect differences between the baseline and 6-month measurements, with the level of significance of .05. Results: After 6 months, the treatment produced a statistically significant reduction in PD and a significant gain in RVCAL and RHCAL, but no observable change in RGMP. RVCAL ranged from 13.77 (± 1.31) at baseline to 12.15 (± 1.29) after 6 months, with a mean change of −1.62 ± 1.00 mm (P .05). RHCAL ranged from 5.54 (± 0.75) to 2.92 (± 0.92), with a mean change of −2.62 ± 0.63 mm (P .05). After 6 months, 76.92% of the patients improved their diagnosis to Class I furcation defects while 23.08% remained as Class II. Conclusion: The present study has shown that positive clinical results may be expected from the combined treatment of Class II furcation defects with EMD and βTCP/HA, especially considering the gain of horizontal attachment level. Despite this result, controlled clinical studies are needed to confirm our outcomes. Keywords: Class II furcation defects, enamel matrix protein derivative, periodontal regeneration, synthetic bone substitute