Intravenous immunoglobulin (IVIg) is administered both for the treatment of immunodeficiencies and for an expanding list of autoimmune diseases. Most adverse effects are mild and transient including headaches, flushing, fever, chills, fatigue, nausea, diarrhea, blood pressure changes and tachycardia. IgA deficiency-related anaphylactic reactions are largely preventable. Late adverse events are rare and include acute renal failure and thromboembolic events. Acute renal failure, usually oliguric and transient, occurs generally in insufficiently hydrated patients and with sucrose-stabilized products due to osmotic injury. Thromboembolic complications occur due to hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic events, immobilization, diabetes mellitus, hypertension, dyslipidemia or those receiving high-dose IVIg in a rapid infusion rate or excessive dose. Slow infusion rate and good hydration may prevent renal failure, thromboembolic events and aseptic meningitis. In our experience in more than 200 patients receiving IVIg for different autoimmune diseases and near 10000 infusions for relapsing-remitting multiple sclerosis patients, the occurrence of adverse effects was 24-36% after high dose IVIg, most were headaches and all were mild adverse events. We conclude that IVIg is a safe therapy when given in a slow infusion rate in well-hydrated patients, better avoiding patients with known risk factors.