Objectives: To evaluate the influence of furcation anatomy and bone defect morphology on the treatment of Class II proximal furcations treated with enamel matrix derivative (EMD) proteins. Method and Materials: Eighteen Class II proximal furcations were treated with open-flap debridement + 24% EDTA conditioning + EMD proteins. Probing depth, gingival margin position, relative vertical and horizontal clinical attachment level, and vertical and horizontal bone levels were evaluated immediately before and 6 months after the surgeries. The changes in these parameters were correlated with vertical defect depth, number of walls, depth defect, interdental distance, root divergence, furcation distance, horizontal measure, root trunk, and furcation height, using the Pearson and Spearman rank correlation tests (α = 5%). Results: The depth defect correlated with gingival margin position (r = 0.52; P = .03), probing depth (r = 0.63; P = .005), and horizontal bone level (r = -0.46; P = .05). The furcation height also correlated with gingival margin position (r = 0.53; P = .02) and horizontal bone level (r = -0.57; P = .01). Moreover, the number of walls of vertical defect positively influenced relative vertical clinical attachment level (r = 0.47; P = .05). Conclusions: Within the limits of this study, furcation anatomy and defect morphology influence the clinical response of EMD protein therapy in Class II proximal furcation involvements. Keywords: clinical trial, enamel matrix derivative proteins, furcation lesions, furcation treatment, periodontal regeneration