INTRODUCTION: Helicobacter Pylori (H. Pylori) is a commonly identified pathogen in cases of dyspepsia. The treatment involves initial eradication, with salvage therapies reserved for refractory cases. Here we report a case of difficult to treat H. Pylori infection associated with gastrointestinal telangiectasias. CASE DESCRIPTION/METHODS: A 20-year-old male presented to our clinic with complaints of persistent dyspepsia, heartburn, and 4 kg weight loss for the last 3 months despite taking proton pump inhibitors (PPI). Initial blood tests were normal. An endoscopy was performed which showed hyperemic mucosa in the body and antrum of the stomach along with multiple telangiectasias in fundus and body of the stomach (Figure 1). Biopsies were performed which showed H. Pylori infection and chronic active gastritis. The patient denied any blood in stools and there was no similar problem in the family as well. The patient was given a two weeks course of PPI, amoxicillin, and clarithromycin. His symptoms improved a little bit during the course. Two weeks after the completion of therapy, his stool for H. Pylori antigen was checked for the confirmation of eradication, which came back positive. He was then prescribed salvage therapy comprising of PPI, amoxicillin, and levofloxacin for 2 weeks. After 1 month of completion of eradication therapy, his stool for H. Pylori antigen was re-checked, however, it again came back positive. He is on high dose PPI and his symptoms have improved, but not completely resolved. DISCUSSION: H. Pylori is a frequent infective cause of gastrointestinal pathologies. The initial eradication therapy involves a combination of PPI and antibiotics. For refractory cases, salvage therapy is recommended. The two proposed regimens include bismuth-containing quadruple or triple therapy including levofloxacin. This case signifies the growing resistance to available therapies and the need to look for new treatment options.Figure 1a.: A single telengiectasia seen in middle third of esophagus b. Telengiectasia seen in body of stomach c. Multiple small sized telengiectasias seen in the gastric fundus.