The aim of this study is to assess the safety and feasibility of autologous peripheral hematopoietic stem cell transplantation in patients with systemic sclerosis, following patient conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. Treatment resulted in improvement in skin thickness and forced vital capacity and pulmonary function for up to 2 years. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be considered, as this can be life-threatening.