Ceftriaxone is a commonly used third-generation cephalosporin with a wide antibacterial spectrum and a long elimination half-life to only dosing once-daily. However, biliary sludge has been reported in patients (including children and adults) who received ceftriaxone therapy. This is a case of an 80-year-old man who was treated with intravenous ceftriaxone 1 g every 12 hours for wound infection. After 3 days of therapy, total and direct bilirubin levels increased significantly, and the patient became jaundiced. Although there are many factors that may cause biliary sludge, we concluded that the case is highly related to ceftriaxone.Clinicians need to be aware of the association of ceftriaxone and hyperbilirubinemia, and monitoring of biochemical laboratory data is necessary.