This study aimed to prospectively evaluate the safety of endoscopic resection for early neoplasia in Barrett's esophagus (BE) using the endoscopic cap resection (ER cap) technique. All resections performed between September 2000 and March 2006 with the ER-cap technique in patients with BE were included. Complications were classified 'acute' (during the procedure) or 'early' (< 48 h after the procedure). A total of 216 ER-cap procedures were performed in 121 patients, of which 145 were performed with a standard hard cap and 71 with a large flexible cap. Specimens removed with the standard cap had a mean diameter of 20 mm (SD 5.0) versus 23 mm (SD 5.8) for the large cap (P < 0.001). Acute complications occurred in 51 procedures (24%), 49 bleedings and two perforations. All bleedings were effectively treated with hemostatic techniques and classified as mild complications. No patient experienced a drop in hemoglobin levels or required blood transfusions or repeat interventions. The two perforations were classified as severe complications and treated conservatively. Three (1%) early complications, all bleedings, occurred and were effectively treated with endoscopic hemostatic techniques and classified as moderately severe complications. In manova the indication for the resection (high-grade intraepithelial neoplasia or early cancer versus low-grade intraepithelial neoplasia or no dysplasia) was found to be significantly associated with an increased risk of acute bleeding. Endoscopic cap resection in BE is safe. Most complications become apparent immediately during the procedure and can be managed endoscopically. Bleeding after the endoscopic resection procedure and severe acute complications (i.e., perforations) are rare (2%).