To describe oral cavity changes in patients who underwent a hematopoietic stem cell transplantation (HSCT). A group of 32 patients was studied after a mean period of 48.8 months (±11.22) from HSCT; oral, dental, and periodontal status were collected and compared with those of healthy matched controls. Unstimulated whole salivary flow (UWS) and salivary pH were also measured. A validated questionnaire (EORTC QLQH&N-35) was used for reported quality of life. Fifty-nine percent of patients were affected by chronic graft-versus-host disease (cGVHD). Dental health and periodontal status were statistically worse than in controls (P = .003 and P = .008, respectively). Regarding the HSCT group, UWS was statistically lower, and EORTC QLQH&N-35 significantly higher than those reported in controls (P = .000 for both). There was no statistical correlation between hypo-salivation and conditioning, presence of cGVHD, type of medication used before and after transplantation, and time of follow-up. A reduction in salivary pH has been noted only for patients with erosive oral lesions. The oral cavity of HSCT patients appeared to undergo substantial modifications and the quality of life was deeply compromised.