Tumor mutation burden(TMB)-High is known to potentially elicit a favorable response to immune checkpoint inhibitors. In this report, we present a case of recurrent hilar cholangiocarcinoma with TMB-High, in which we performed comprehensive treatment including immune checkpoint inhibitor pembrolizumab. The patient was a 58-year-old male diagnosed with hilar cholangiocarcinoma who underwent extended right hepatectomy, caudate lobe resection, bile duct excision, and bile duct reconstruction. Postoperatively, peritoneal seeding recurrence and liver metastasis were observed, indicating TMB-High. Therefore, pembrolizumab therapy was administered. The tumor marker CA19-9 significantly decreased, and the peritoneal seeding and liver metastatic lesions disappeared on imaging. In this case, we experienced the use of pembrolizumab monotherapy for TMB-High recurrent bile duct cancer with early postoperative peritoneal seeding recurrence. Further accumulation of cases is needed, but pembrolizumab monotherapy holds promise as a treatment option for TMB-High bile duct cancer at the hepatic hilum.