The aim of the present study was the evaluation of the efficacy of open flap debridement (OFD) with and without enamel matrix derivatives (EMD) in the management of class II furcation involvement. Twenty similar bilateral class II furcation defects in ten healthy nonsmoker patients were selected. One defect in each subject was treated with OFD alone (OFD group) and the contralateral one with OFD and simultaneous application of enamel matrix derivatives (EMD group). Clinical probing depth, vertical clinical attachment level, horizontal clinical attachment level, and the location of the gingival margin, horizontal probing depth of bony defect (E-HPD), vertical depth of bone crest, vertical depth of the base of bony defect (V-DBD), and length of the intrabony defect were measured at baseline and during reentry surgery after 6 months. Wilcoxon signed-rank test and Mann-Whitney U test were used to analyze the data. Among soft tissue parameters, only horizontal attachment gain in EMD was significantly more than OFD (P = 0.002). Application of EMD significantly enhanced the horizontal (E-HPD) and vertical (V-DBD) resolution of the bony defect (P < 0.05). In conclusion, it seems that the adjunctive use of EMD enhances the efficiency of OFD in the management of mandibular class II furcation defects.