AIM:To introduce and evaluate the efficacy and technical aspects of endoscopic submucosal dissection(ESD) using a novel device,the Fork knife.METHODS:From March 2004 to April 2008,ESD was performed on 265 gastric lesions using a Fork knife (Endo FS(R)) (group A) and on 72 gastric lesions using a Flexknife (group B) at a single tertiary referral center.We retrospectively compared the endoscopic characteristics of the tumors,pathological findings,and sizes of the resected specimens.We also compared the en bloc resection rate,complete resection rate,complications,and procedure time between the two groups.RESULTS:The mean size of the resected specimens was 4.27 + 1.26 cm in group A and 4.29 + 1.48 cm in group B.The en bloc resection rate was 95.8%(254/265 lesions) in group A and 93.1% (67/72) in group B.Complete ESD without tumor ceil invasion of the resected margin was obtained in 81.1% (215/265)of group A and in 73.6% (53/72) of group B.The perforation rate was 0.8% (2/265) in group A and 1.4%(1/72) in group B.The mean procedure time was 59.63 + 56.12 min in group A and 76.65±70.75 min in group B (P ＜ 0.05).CONCLUSION:The Fork knife (Endo FS(R)) is useful for clinical practice and has the advantage of reducing the procedure time.