When a patient is undergoing a biliary tract procedure such as percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopan-creatography (ERCP), or open or laparoscopic surgical operations, preprocedural antibiotic treatment is indicated. When selecting appropriate antibiotic coverage it is crucial to look at local institutional microbiological profiles as well as identifying risk factors for bacterobilia. For low-risk patients, namely those who are not severely ill, have not had previous biliary procedures, and have community-acquired illness, a one-time preprocedural treatment with 1 g of cefotetan intravenously (IV) or a fluoroquinolone IV with additional anaerobic coverage with metronidazole 500 mg IV is sufficient, with no proven benefit for postprocedural antibiotics. In patients who are severely ill, with previous instrumentation or hospital-acquired illness, broader-spectrum treatment with piperacillin/tazobactam 3.375 mg IV or a fluoroquinolone with additional anaerobic coverage is indicated. A one-time dose is sufficient, except in cases where adequate drainage is not achieved or in cases of sepsis or cholangitis, where anywhere from 5 to 14 days of treatment may be required.