This work sought to investigate the clinical efficacy of esterified hyaluronic acid for treating deep periodontal defects. Nineteen defects, 18 infrabony and one mandibular molar furcation, were treated. Defects with probing pocket depths (PPDs) of at least 6 mm were consecutively included in the study. The PPD, gingival recession, and clinical attachment level (CAL) were evaluated at each defect before treatment and 1 year after surgery. A full-thickness flap was raised and the roots were accurately planed; hyaluronic acid in the form of fibers was then packed into the defect to completely fill the space. One year after treatment, the mean PPD was reduced by 5.8 mm (range, 0 to 10 mm), gingival recession had increased by 2.0 mm (range, 0 to 6 mm), and attachment gain was 3.8 mm (range, 0 to 7 mm).