Tooth extraction in patients treated with bisphosphonates (BPs) for osteoporosis or cancer exposes the patient to the risk of osteonecrosis of the jaw. An autologous membrane using platelet-rich fibrin (PRF) is an innovative technique to promote wound healing, which allows obtaining a hermetic closure of the post-extractive surgical site without the need of mucoperiosteal flaps or periosteal releasing incisions. Here, we report the case of a 70-year-old woman, in therapy with alendronate for 12 years, requiring the upper right premolar extraction because of a crown fracture. After the tooth extraction performed under antiseptic and antibiotic coverage, the PRF autologous membrane was placed on the surgical wound to close completely the post-extraction site. Follow-up visits were carried out after one, two, four weeks and two months from the intervention. The complete re-epithelization of the wound was observed without signs of infection. The use of PRF for the closure of post-extraction sockets in patients taking BPs appears to be a promising alternative to the more invasive surgical procedures. Future clinical trials will be pivotal in elucidating the effectiveness of PRF to prevent BP-related osteonecrosis after tooth extraction.