Objectives. Cementogenesis seems to be significantly compromised during tissue inflammation. In dental practice, surgical procedures are performed with the aim to regenerate periodontium including cementum. However, inflammation that occurs during the initial healing phases after surgery may impair regeneration of this tissues. The aim of the present study was to assess if surgical procedures designed to regenerate periodontium might affect levels of cementum protein-1 (CEMP-1) in periodontal wound fluid during early phase of healing. Materials and Methods. In 36 patients, 18 intrabony periodontal defects were treated with regenerative therapy (REG group) and 18 suprabony periodontal defects were treated with open flap debridement (OFD group). In the experimental sites, gingival crevicular fluid was collected immediately before surgery, and periodontal wound fluid was collected 4, 7, 14, and 21 days after surgery. CEMP-1 levels were detected by indirect enzyme-linked immunosorbent assay technique. Results. At the analysis, it resulted that there was a significant average difference in CEMP-1 values between the REG and OFD groups at baseline (p=0.041), the CEMP-1-modeled average in the OFD group was lower by 0.45 ng/ml. There was a significant trend in CEMP-1 over time, and this trend was different among the 2 groups: the REG group showed a statistically significant rising CEMP-1 trend (0.18 ng/ml a week p=0.012), while the OFD had a trend that was significantly lower (-0.22 ng/ml a week compared to the REG group trend p=0.023), the OFD group lost on average 0.05 ng/ml a week. In REG sites, GCF protein levels resulted also related to clinical parameters. Conclusions. During the initial inflammatory phase of periodontal healing, CEMP-1 levels decrease regardless of the surgical protocol applied. The surgical procedures used to regenerate periodontal tissue are able to reverse this trend and to induce significant increase of CEMP-1 in periodontal wound fluid after the first week postop.