Background and Aims : Various societies have published guidelines on managing antithrombotic agents during the periendoscopic period. Management of anticoagulants in high-risk procedures is similar among these guidelines : however, management of antiplatelet agents in low-risk procedures such as biopsy differs between Western and Japanese guidelines. Therefore, we conducted a clinical study to assess the bleeding risk attributable to upper gastrointestinal biopsy in patients taking antiplatelet agents and the validity of performing endoscopic biopsy with small cup biopsy forceps. Methods : We changed the management of antithrombotic agents during the periendoscopic period in our hospital as follows : esophagogastroduodenoscopy was performed without cessation of antithrombotic agents and biopsy with small cup biopsy forceps was permitted in patients taking antiplatelet agents. Then, a prospective cohort study in a clinical setting was performed from March 2011 to February 2012 for 5,374 scheduled esophagogastroduodenoscopies. 1,128 patients, including 65 who were taking antiplatelet agents, underwent gastric biopsy, and 2,025 biopsy specimens were obtained from each part of the stomach. Clinical bleeding was investigated during and after endoscopy. Two pathologists assessed the presence of muscularis mucosae in biopsy specimens in addition to the suitability of specimens for histological diagnosis. Results : Ratio of appropriate specimens obtained with small cup biopsy forceps was 99.3% (2,010/2,025) and muscularis mucosae was detected in 27.8% (538/1,394) of specimens. After endoscopy, 1 of 1,049 patients who took no antithrombotic agents experienced major bleeding (0.095%). In addition, no bleeding was experienced by the 65 patients who received antiplatelet treatment. Conclusions : Endoscopic forceps with a small cup is useful and the absolute risk attributable to gastric biopsy in patients taking antiplatelet agents seems to be low.