Intravenous immunoglobulin (IVIg) is a potential alternative treatment for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) with less toxicity than conventional immunosuppressive agents. This randomized, placebo-controlled trial aimed to investigate the efficacy of a single course of IVIg (total dose 2 g/kg) in previously-treated AASV with persistent disease activity in whom there was an intention to escalate therapy. Vasculitic activity was monitored by the Birmingham vasculitis activity score (BVAS), C-reactive protein (CRP) and ANCA levels. Treatment response was defined as a reduction in BVAS of more than 50% after 3 months, and there was an intention to keep doses of concurrent immunosuppressive drugs unchanged during this period; follow-up continued to 12 months. Seventeen patients were randomized to receive IVIg and 17 to receive placebo. Treatment responses were found in 14/17 and 6/17 of the IVIg and placebo groups, respectively (p=0.015, OR 8.56, 95%CI 1.74-42.2). Following infusion of trial medication, greater falls in CRP were seen at 2 weeks (p=0.02) and 1 month (p=0.04) in the IVIg group. No differences were observed between ANCA levels or cumulative exposure to immunosuppressive drugs, and after 3 months there were no differences in CRP levels or disease activity between the IVIg and placebo groups. Seventeen adverse effects occurred after IVIg and six after placebo: they were mostly mild, although reversible rises in serum creatinine occurred in four from the IVIg group. A single course of IVIg reduced disease activity in persistent AASV, but this effect was not maintained beyond 3 months; mild, reversible side-effects following IVIg were frequent. IVIg is an alternative treatment for AASV with persistent disease activity after standard therapy.