Large sessile colorectal polyps represent a treatment challenge. Nowadays there are discrepancies regarding how to proceed with them because of morbidity, the possibility of incomplete endoscopic resection, and the high possibility of a coexisting malignancy. This study was performed to determine the safety and effectiveness of endoscopic removal of sessile colorectal adenomas larger than 4 cm. Seventy-four patients with a total of 74 sessile polyps larger than 4 cm in diameter were treated endoscopically. Polyps were removed using argon plasma coagulation (APC) as an adjunct to piecemeal technique. Surgery was recommended in patients with invasive neoplasia. Patients with favorable histology (low-grade dysplasia [LDG] or high-grade dysplasia [HGD]) were followed up with monthly endoscopies untill total ablation of the lesion, and then at 3- to 6-month intervals. LGD was found in 38 patients, HGD in 24, and invasive neoplasia in the remaining 12 patients. A total of 54 patients were followed up for at least 6 months. Recurrence rate of polyps with favorable histology was 9.2% (5/54). Postpolypectomy bleeding was the only complication, observed in 10 patients (13.5%). We conclude that piecemeal polypectomy plus APC without saline injection, performed by an expert endoscopist, is a safe and effective treatment for all LGD or HGD large sessile colorectal polyps.