Objectives: To gain insight into the experiences of patients with diffuse cutaneous systemic sclerosis during and after autologous hematopoietic stem cell transplantation. Methods: Semi-structured interviews were conducted with patients who underwent hematopoietic stem cell transplantation in four university hospitals in the Netherlands. Interviews were transcribed verbatim and thematically analyzed. Results: Nine male and seven female patients were interviewed, median age 47 years (range: 27–68). Patients mentioned their life was severely disrupted before hematopoietic stem cell transplantation and remained unsettled a long time after treatment. Uncertainty because of disease progression, loss of control over health and the sense of time and fear of treatment-related adverse events were common during hospitalization. After hematopoietic stem cell transplantation, patients experienced more physical limitations than they had expected, and recovery took longer and was mentally taxing. Going back to work and finding a new balance in personal relations and social life was complicated. Patients described various strategies to deal with challenges. Family and friends provided essential support, although many experienced a dwindling social circle. Most patients also appreciated peer support. All patients were satisfied with the low threshold for contact with physicians and nurses during hospitalization. However, aftercare focused on medical aspects rather than on psychological well-being and social issues. Moreover, patients would have preferred to be better prepared on what to expect after discharge, and lacked information about self-management, prognosis, optimal recovery, work, sexuality, and family planning. Conclusion: Hematopoietic stem cell transplantation has a major physical and psychological impact on patients with diffuse cutaneous systemic sclerosis. The course of recovery after this intensive therapy was unexpectedly long for some patients and offer of support was far less pro-active post-HSCT compared to pre-HSCT and during HSCT.