Adult-onset hypertrophic pyloric stenosis (HPS) is a rare anomaly that can be idiopathic or related to underlying gastric pathology. We describe a case of a 25-year-old man with history of human immunodeficiency virus and osteoglophonic dysplasia who presented with pain and swelling at a gastrostomy site. Computed tomography and upper gastrointestinal barium swallow demonstrated gastric distention and stricture at the distal portion of the gastric antrum. An ultrasound detected HPS. The patient eventually required pyloromyotomy for treatment. Human immunodeficiency virus infection has numerous gastrointestinal ramifications, but HPS has not been identified as one. Osteoglophonic dysplasia has not been an established risk factor for HPS. Idiopathic HPS is extremely rare in adults, but should be considered in this population when patients present with gastric outlet obstruction.