Oral and topical sucralfate is regularly used in ulcers of gastrointestinal tract, vaginal and perianal excoriations, and radiation burns. This study was designed to determine whether there was any advantage of topical application of sucralfate in reducing postoperative pain and promoting wound healing after open hemorrhoidectomy in patients with Grades III or IV hemorrhoids. A total of 116 patients were randomly assigned to receive sucralfate cream (sucralfate group) or placebo cream (control group) applied to the surgical site. Weekly pain score was evaluated by using Visual Analog Scale. The amount of analgesic tablets consumed in each week also was assessed. At the end of four weeks, two independent surgeons assessed the wound healing. There was no significant difference in age, gender distribution, and number of excised hemorrhoid piles between the two groups. Patients in the topical sucralfate group experienced significantly less pain at Day 7 (Visual Analog Scale +/- standard error of the mean, 3.7+/-0.3 vs. 6.1+/-0.7; P<0.002) and at Day 14 (1.6+/-0.2 vs. 3.1+/-0.6; P<0.01). Likewise patients who received sucralfate cream used less analgesic tablets compared with the placebo group. In the sucralfate group, the overall wound healing ranked significantly better than in controls (P<0.02). Topical sucralfate significantly reduces pain at Days 7 and 14 after hemorrhoidectomy and promotes faster wound healing compared with that of a placebo.