The aim of the present study was to evaluate, clinically and via CBCT, the long-term efficacy of a bioresorbable polylactic acid membrane combined with deproteinized bovine bone graft (DBBM) and compare it to enamel matrix derivative (EMD) combined with DBBM graft in the treatment of class II furcation defects. Sites were randomly assigned to the test group (Guidor Matrix Barrier + Bio-Oss) or the control group (Emdogain + Bio-Oss). Probing pocket depth (PPD), clinical attachment level (CAL), gingival recession (REC), and keratinized tissue (KT) width were assessed at 12 and 24 months, and radiographic bone gain was investigated at 24 months via CBCT. Both groups showed a significant radiographic bone fill and clinical gain. The combination of Emdogain + Bio-Oss showed better clinical outcomes and less complications, though this difference was not statistically significant.