We describe the case of a patient for whom choledochoduodenostomy was performed under endoscopic ultrasound (EUS) guidance as an alternative to percutaneous transhepatic biliary drainage (PTBD) for the treatment of obstructive jaundice. An 82-year-old man with ampullary cancer was considered operable, but he refused surgery. Endoscopic biliary drainage (EBD) with an 8.5- French plastic stent was performed 2 months later because of the development of obstructive jaundice. The EBD stent was occluded 5 months after the stent insertion, and EUS choledochoduodenostomy (EUS-CDS) was performed. Pneumoperitoneum occurred 1 day after the procedure, which resolved with conservative treatment. Six months later, multiple lymph node metastases occurred, and the patient was effectively treated by chemotherapy (S-1). The patient is still alive with a good quality of life more than 2 years after EUS-CDS. We conclude that EUS-CDS is an effective alternative to PTBD or EBD for patients with malignant biliary obstruction, especially due to ampullary cancer.