Five patients with obstructive jaundice caused by malignant periampullary biliary stenosis underwent EUS-guided choledochoduodenostomy (EUS-CDS) from the first portion of the duodenum using a convex echoendoscope and a needle knife. All the steps of the procedure including passage dilatation and the plastic stent placement were performed through the accessory channel of the echoendoscope over the guide wire. Stent insertion was technically successful in all five patients. The procedure was also clinically effective in relieving jaundice in all cases. One patient developed pneumoperitoneum, which resolved with conservative management. Stent exchange was successful in seven of eight attempts in patients with stent occlusion. One failure was due to tumor invasion to the choledochoduodenal fistula. Stent patency was maintained in the remaining patients throughout their survival period. The average stent patency was 211.8 days. EUS-CDS from the first portion of the duodenum appears to be feasible and safe in cases of obstructive jaundice caused by distal bile duct obstruction.