The etiology of hypertrophic pyloric stenosis (HPS) is still unclear. The case under study was a 28 day old boy apparently with Down syndrome who had been suffering from projectile vomiting for three days before admission without any defecation during this period. In physical examination, abdominal distention was observable but there was not a remarkable olive sign. Ultra-sonographic findings showed that pyloric channel length and muscle thickness were 28 mm and 4 mm respectively. For further evaluation, upper gastrointestinal radiography was done, which proved that there was a relative obstruction. Despite supportive treatment and complete resuscitation, vomiting did not stop. Since there was the clinical suspicion that the patient's problem was HPS, an operation was performed on him .In the operation it was found that annular pancreas coexisted with HPS. Pyloromyotomy Fredet-Ramstedt and pancreas bands release were performed. Three days after the surgery and following resuming oral feeding, the neonate was discharged in a good general condition. Occurrence of annular pancreas with HPS in the patient can suggest the existence of prenatal resistance to gastric emptying, as an etiologic factor in HPS. However, further study is needed to approve this hypothesis.