Oral mucositis (OM) may occur in up to 100% of patients undergoing condition regimen to hematopoietic stem cell transplant (HSCT). From the patients perspective, OM is one of the most debilitating side effects of transplantation. It is commonly thought that oral hygiene can modify the incidence and severity of oral mucositis, therefore professional oral health care (POHC) is recommended prior to conditioning regimen for HSCT. A new strategy for the treatment of OM is sodium hyaluronate (SH) combined with amino acid precursors of collagen (Aas) (Mucosamin®). SH is a mucoaderent polymer acting as a mechanical barrier and pain reliever. Furthermore, it allows prolonged contact of the product with the mucous membrane. In this study, a total of 68 adult patients due to undergo HSCT for allogenic and autologous transplant were enrolled at the Stem Cell Transplant Unit. The patients were divided into two groups. One group was treated with POHC before HSCT and applications of Mucosamin® during the recovery after transplantation. The second group served as controls, with the usual treatment of Clorexidine 0.20% adopted by the department. After HSCT the same clinician, an expert in oral medicine trained for the clinical trial, evaluated symptoms of the patients mucositis of both groups every day. The treated patients developed less severe OM, therefore Mucosamin® seems to have a protective role against the more severe phases of mucositis. The maximum OM pain, measured with the VAS scale, was higher in patients who did not use Mucosamin®. In the treated group OM resolved sooner than in the control group.