Use of collagen membrane (CM) with deproteinized bovine bone mineral (DBBM) and enamel matrix derivative (EMD) in periodontal regenerative therapy was evaluated. A total of 40 intrabony defects in periodontitis patients were treated. Clinical parameters and filled bone volume (FBV) and rate (FBR) were assessed. Probing pocket depth (PPD) was reduced significantly at 12 months with CM treatment, while clinical attachment level (CAL), FBV, and FBR showed similar improvements. In stratified analyses, CM-treated thick-biotype patients showed significant improvement in PPD and CAL. Regenerative therapy with the use of EMD and DBBM showed similar improvements in periodontal tissue regeneration with or without CM. The combination with CM appeared to influence the healing of soft tissue and was effective in decreasing pocket depth.