A multicenter prospective consecutive case series study was conducted to evaluate the effectiveness of placental allografts to correct moderate to severe buccogingival recession defects. Nineteen healthy patients, 13 women and 6 men, ranging in age from 29 to 63 years, with 43 maxillary and mandibular gingival recession defects of > 4 mm deep were included. Clinical examination at multiple postsurgery time points revealed healthy maturation of gingival tissues with normal color and texture matched to adjacent soft tissue areas. Complete root coverage was not achieved in all cases in this proof of principle evaluation. Severe buccal bone loss had occurred in most of the selected cases, which may have negatively influenced the results. Nonetheless, it was possible to achieve root coverage and demonstrate gain in clinical attachment level and height of keratinized tissue when placental allograft was used. Future randomized clinical trials are needed to further explore the potential of placental allografts for treatment of localized gingival recession defects.