In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater.