Cryoglobulins are circulating immune complexes that precipitate at cool temperatures and can induce a small-vessel vasculitis. While patients with endocarditis are well known to have circulating cryoglobulins, cryoglobulinemic vasculitis is a rare complication of infective endocarditis with infrequent publication of reported cases. We present two cases of methicillin-resistant Staphylococcus aureus tricuspid valve infective endocarditis in patients with substance use disorder complicated by cryoglobulinemic cutaneous vasculitis confirmed by skin biopsy, including one patient who developed renal and colonic manifestations of vasculitis. Both patients had symptomatic improvement in their vasculitis with appropriate antimicrobial therapy, including one patient who received a short course of prednisone and another with chronic active hepatitis C that remained untreated. Providers should have a high-index of suspicion for infective endocarditis in patients presenting with new onset cryoglobulinemic vasculitis, particularly if the patients have underlying risk factors for endocarditis.