Transient esophageal ulceration is a common finding after sclerotherapy of varices. A small proportion of these ulcers become chronic and resistant to conventional therapy. Such chronic ulcers have been associated with pain, stricture formation, and recurrent hemorrhage. The use of omeprazole, a proton pump inhibitor, was examined in the current study in the treatment of 10 patients (6 women, 4 men; age range, 27-86 years) with cirrhosis (PBC, 4; sclerosing cholangitis, 2; chronic active liver disease, 2; alcohol, 1; and cryptogenic, 1) who developed an esophageal ulcer after a mean of 13 (range, 8-21) sessions of sclerotherapy. The ulcers had been present for 3-54 months despite prolonged treatment with high-dose H2-receptor antagonists and sucralfate. In each case one or more complications had occurred: severe pain in 3, stricture formation in 4, and recurrent hemorrhage in 7 cases. After an 8-week course of omeprazole, 40 mg daily, endoscopy confirmed complete healing of the ulceration in all 10 cases with symptom resolution. In 2 cases the ulcer recurred, with associated bleeding within 6 weeks of discontinuing the treatment in 1 patient. Both cases responded to repeat therapy. These results confirm the efficacy of omeprazole for postsclerotherapy ulceration and imply that acid-pepsin has a role in perpetuating such ulcers. © 1990.