AIM We introduce a new highly selective vagotomy (HSV) procedure which can completely destroy anyexisting variant vagal fibers innervating the proximal stomach.METHODS Twenty-eight dogs were divided into three groups: group A had retrograde liberated highlyselective vagotomy (RLHSV), group B had traditional HSV and group C as control group. Gastric acidsecretion function was tested and gastric parasympathetic and sympathetic enervation were studied byretrograde tracing the horseradish peroxidase (HRP) or by histochemical staining. After being convincedthat the modified procedure was an easier and more effective HSV on animal model, we applied thetechnique to the treatment of duodenal ulcers in 100 patients.RESULTS Significant decrease of acid secretion was found in operated dogs in both group A and B. After injection of HRP subserously into the fundus and body, no HRP positive cells were found in the vagal dorsalnucleus in group A and B but were in group C. When HRP was injected into the antrum, HRP stained cellswere found in dorsal nucleus in all three groups. The negative histochemical staining of AchE and the positivefluorescence in the fundus and body in group A and B indicate that parasympathetic nerve fibers weredestroyed completely while norepinephrinergic nerve fibers were intact. When the operation was applied topatients, no severe complications or operative mortality occurred. Patients were followed up for 6- 84months. They all had complete gastric emptying function. Ninety-four patients were graded as Visick I orⅡ. Six as Visick Ⅲ and Ⅳ. Eighty patients had been followed up with gastroscopy for two years afteroperation. Four patients had recurrent ulcers. Among them two patients were asymptomatic and the othertwo had symptoms and were treated with partial gastrectomy.CONCLUSION Compared to the classic HSV, our modified procedure is more effective clinically andconvenient technically.