PURPOSE The purpose of the study was to determine the variables associated with postoperative pain and the clinical response of patients with uncomplicated hemorrhoidal disease treated with stapled rectal mucosectomy in the medium term. METHODS Patients with Grade II to IV, uncomplicated hemorrhoidal disease who underwent stapled rectal mucosectomy were prospectively included. The basal characteristics of the population were evaluated and level of stapling and placement of hemostatic suture determined. Histologically, the type of resected epithelium and presence of muscle fibers was evaluated. Postoperative pain was evaluated by means of a visual analog scale. Complications and clinical response were evaluated. RESULTS One hundred patients with a mean age of 43.9 years were included. Only columnar epithelium was resected in 48, transitional epithelium in 47, and squamous epithelium in 5 patients. Smooth muscle fragments were found in 55 patients, and, in 12 of these, fibers from the external muscular layer of rectum were also seen. Follow-up was 12.6 +/- 3.4 (range, 7-24) months. A total of 79 patients were completely asymptomatic at the end of follow-up. Resected squamous epithelium was associated with a higher postoperative pain level in the multivariate analysis (coefficient beta = 1.16 (95 percent confidence interval, 0.08-2.24); P = 0.035). CONCLUSIONS Rectal mucosectomy with stapler is an effective method for the treatment of uncomplicated prolapsing hemorrhoidal disease. Intensity of postoperative pain was associated with the type of resected epithelium. This suggests that low transection of hemorrhoids must be avoided.