Aim. To determine the possible boundaries of high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HDIT-autoHSCT) for autoimmune diseases (AUDs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Subjects and methods. A long-term trial was conducted at one center to evaluate the efficiency and safety of HDIT-autoHSCT in patients with AUDs. The previous standard therapy was noted to be resistant or lowly effective. The age of 10 patients with systemic connective tissue diseases was 27.6±2.8 years; the pre-HDIT-autoHSCT disease duration was 5.9±1.3 years; the median posttransplantation follow-up was 39.3 months. The age of 49 patients with MS reached 34.9±1.33 years; the pretransplantation disease duration was 8.4±0.69 years; the median post-HDIT-autoHSCT follow-up was 42 months. The efficiency of transplantation was evaluated on the basis of clinical findings, by using scales, laboratory tests, and magnetic resonance imaging. Pretransplantation conditioning was carried out according to the protocols: a) BEAM + antilymphocyte globulin (ALG); b) fludarabine + melphalan + ALG. No fatal outcomes due to a transplant procedure were observed. Results. Overall 5-year survival after transplantation was 80% for systemic connective tissue diseases and 95% for MS; 5-year progression-free survival rates were 30% in the RA and SLE groups and 45% in the MS group. HDIT-autoHSCT turned out safe and reduced the activity of the process and further disease progression for a long period of time, as confirmed by regression of clinical symptoms and/or status stabilization in 9 patients with SLE or RA and in all patients with MS. Conclusion. The favorable factors associated with the results of transplantation are age younger than 35 years in collagenoses with their short-term duration and moderate signs; age younger than 40 years in MS with a disease duration of less than 10 years and expanded disability status scale scores of not more than 6.5. Of importance are functional system scores, duration of first remission, and an index of disease progression in different types of MS.