Extra hepatic manifestations of chronic hepatitis C (HCV) include type II cryoglobulinemia. Previous studies suggest pegylated interferon (Peg-INF) plus ribavirin (RBV) is an effective treatment for HCV related type II cryoglobulinemia [1–4]. The current clinic use of triple therapy is in its second year and the landmark phase 3 clinical trials for telaprevir and boceprevir showed substantial improvements in efficacy for the treatment of genotype 1 HCV [5–9]. However, there are minimal data on the safety and efficacy of triple therapy for HCV-related type II cryoglobulinemia. Cryoglobulins are detectable in 40–70 % of patients with HCV [10, 11], and overt vasculitis develops in 5–10 % of patients [12]. Cryoglobulin associated vasculitis can lead to neuropathy, skin ulcers, and most notably renal disease in the form of membranoproliferative glomerulonephritis (MPGN) [12, 13]. Renal disease secondary to type II cryoglobulinemia is associated with increased mortality [14]. Treatment of cryoglobulinemia with the antiviral regimen of Peg-INF plus RBV yields cryoglobulin clearance in half of the patients [3]. Treatment with corticosteroids, rituximab and plasmapheresis are employed in the treatment of HCV associated cryoglobulin vasculitis, though with varying long-term success, as these do not eliminate the underlying viral antigen trigger [15, 16]. Likewise, there is concern that prolonged immunosuppression may lead to accelerated HCV-related liver disease and impairment of viral clearance on anti-HCV therapy [17]. Treatment guidelines for genotype 1 HCV now recommend performing a risk–benefit analysis on the individual patient when considering triple therapy [18]. Unfortunately, there is insufficient clinical data when weighing triple therapy risks and benefits in patients with cryoglobulinemia and associated renal disease, especially the impact of reduced renal function on the new protease inhibitors. The initial phase III trial of boceprevir only included patients with a serum creatinine below the upper limits of normal, while telaprevir was only studied in patients with a creatinine clearance (CrCl) greater than 50 ml/min. This would exclude patients with MPGN which had progressed to CKD stage 3b-5; though patients with subclinical renal disease may have participated in clinical trials. In addition, trials for both drugs excluded patients with conditions requiring longterm corticosteroid use [5, 7]. This would likely exclude patients with vasculitic skin ulcers, as this condition is frequently treated with long-term corticosteroids albeit with variable efficacy [19]. Thus we sought to describe the treatment experience of four patients with overt clinical manifestations of MPGN and/or laboratory proven cryoglobulinemia in a case series at one academic clinical center.