To identify which factors can influence the patients' perception of protective isolation following Haematopoietic Stem Cell Transplantation (HSCT).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.The participants were 182 adult patients receiving autologous (48%) or allogeneic (52%) HSCT in protective isolation. Male sex (β = .152), education level (β = -.245), double room (β = .186), satisfaction with visiting hours (β = -.174) and emotional support from nurses (β = -.169) were independently associated with isolation-related suffering. Significant predictors of the relationship with oneself included body temperature (β = -.179), fatigue (β = -.192) and emotional support from nurses (β = -.292). Factors independently associated with the relationship with others were education (β = -.230), chemotherapy cycles (β = -.218), pain (β = .150) and satisfaction with visiting hours (β = -.162).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.