AIM: To evaluate and compare the clinical outcomes of prophylactic submucosal saline-epinephrine injection and saline injection alone for large colon polyps by conventional polypectomy.METHODS: A prospective study was conducted from July 2003 to July 2004 at 11 tertiary endoscopic centers. Large colon polyps (＞ 10 mm in diameter) were randomized to undergo endoscopic polypectomy with submucosal saline-epinephrine injection (epinephrine group) or normal saline injection (saline group).Endoscopic polypectomy was performed by the conventional snare method, and early (＜ 12 h) and late bleeding complications (12 h-30 d) were observed.RESULTS: A total of 561 polyps in 486 patients were resected by endoscopic polypectomy. Overall, bleeding complications occurred in 7.6% (37/486) of the patients,including 4.9% (12/244) in the epinephrine group,and 10.3% (25/242) in the saline group. Early and late postpolypectomy bleeding (PPB) occurred in 6.6%(32/486) and 1% (5/486) of the patients, respectively,including 4.5% (11/244), 0.4% (1/244) in the epinephrine group, and 8.7% (21/242), 1.7% (4/242) in the saline group. No significant differences in the rates of overall, early and late PPB were observed between the 2 groups. Multivariate stepwise logistic regression analysis revealed that large size (＞ 2 cm) and neoplastic polyps were independently and significantly associated with the presence of PPB.CONCLUSION: The prophylactic submucosal injection of diluted epinephrine does not appear to provide an additional advantage over the saline injection alone for the prevention of PPB.