OBJECTIVES: To identify which factors can influence the patients' perception of protective isolation following Haematopoietic Stem Cell Transplantation (HSCT). METHODS: This is a prospective study conducted in 10 Italian centres, members of the Italian Group of stem cell transplant (GITMO). Patients' perception of protective isolation was assessed using the ISOLA scale between 7 and 9 days post-transplant. Statistical linear regression analysis was performed. RESULTS: The participants were 182 adult patients receiving autologous (48%) or allogeneic (52%) HSCT in protective isolation. Male sex (beta = .152), education level (beta = -.245), double room (beta = .186), satisfaction with visiting hours (beta = -.174) and emotional support from nurses (beta = -.169) were independently associated with isolation-related suffering. Significant predictors of the relationship with oneself included body temperature (beta = -.179), fatigue (beta = -.192) and emotional support from nurses (beta = -.292). Factors independently associated with the relationship with others were education (beta = -.230), chemotherapy cycles (beta = -.218), pain (beta = .150) and satisfaction with visiting hours (beta = -.162). CONCLUSION: Healthcare providers should pay greater attention in caring for those patients who are at risk for a negative isolation experience. Nurses should provide emotional support.