Hemorrhoidal banding is a well-established and safe outpatient procedure. Septic complications of hemorrhoidal banding are rare but can be fatal. The first case of pylephlebitis (septic portal vein thrombosis) and pyogenic liver abscess following hemorrhoidal banding in a 49-year-old man with diabetes is reported in the present study. Risk factors, management and the role of prophylaxis in immunocompromised patients are discussed. Caution against hemorrhoidal banding in immunosuppressed patients, including patients with diabetes, is warranted.