As autologous stem cell transplantation (ASCT) is increasingly frequent in some patients with multiple sclerosis (MS), the knowledge of its adverse effects is paramount. Early complications (within 30 from transplantation) are usually due to conditioning regimen and consequent neutropenia. They include infections and noninfectious complications, such as oral and intestinal mucositis, increases in liver enzymes, hemorrhagic cystitis, and worsening of neurologic symptoms. Infections in the early phase, particularly during neutropenia, are mainly of bacterial origin, such as bloodstream infections, pneumonia, central-venous catheter-related infections, urinary infections, and neutropenic typhlitis, followed by viral reactivations. Prophylaxis with acyclovir against reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) is recommended, while a preemptive strategy is used for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) management. Fungal infections are infrequent and mainly caused by Candida, thus fluconazole prophylaxis is used in some centers. Late complications include secondary autoimmune diseases: hematologic, such as immune thrombocytopenic purpura, autoimmune hemolytic anemia, or acquired hemophilia, or nonhematologic, such as thyroiditis, rheumatoid arthritis, or Crohn's disease. Other late complications are endocrinopathies and gonadal dysfunction with possible consequences on fertility. Particularly in women over 32 years of age, the risk of infertility and premature ovarian insufficiency can be significant. Thus, reproductive counseling with fertility preservation techniques if required is mandatory before ASCT.