Introduction: Primary Polycythemia Vera (PPV) is a myelodysplastic disorder associated with thrombotic complications. It is associated with an increased risk of gastrointestinal bleeding (GIB) from peptic ulcer disease. We describe a father and son with PPV and JAK 2 mutations, who presented with GIB due to peptic ulcer disease within a one-year interval. Patient 1: A 32-year-old Asian-American male with PPV treated by regular phlebotomy presented with hematemesis and melena and Hgb of 6.6 mg/dL. No previous history of GIB. Following resuscitation, upper endoscopy revealed a duodenal ulcer with a visible vessel. Hemostasis was achieved using epinephrine injection and hemoclips. The patient denied NSAID use and subsequent H.Pylori antibody testing was negative. Patient 2: A 69-yearold Asian-American, the father of patient 1 who also has PPV treated with phlebotomy and has no previous GIB history. He developed hematemesis 11 months after his son's presentation with a drop in Hgb to 7.6 mg/dL. Upper endoscopy revealed two clean based duodenal ulcers. No high risk stigmata was seen and therefore no therapeutic intervention was necessary and he recovered on medical therapy. His Helicobacter pylori antibody was also negative. Discussion: PPV is classified as a myeloproliferative disorder. Patients with PPV are at risk for both thrombotic and hemorrhagic events. GIB related to PPV is not common, but it can be severe. It is associated with the concurrent use of antiinflammatory agents. Additionally, patients with PPV have been found to have a higher incidence of H. pylori infection. Platelet dysfunction is thought to play an important role in the development of GIB. Thrombocytosis leads to the development of Acquired Von Willebrand syndrome (Type 2 AvWD) by increased proteolysis by ADAMTS 13, leading to bleeding episodes. Sluggish microvascular circulation in the GI tract secondary to increased hematocrit has also been implicated in mucosal ischemia leading to breakdown of protective barriers. Increased basophil mediated histamine release has also been proposed as a potential risk factor. Conclusion: PPV is associated with GIB due to PUD due to multiple factors. A possible strategy to mitigate the risk may be to remove other factors that could contribute to the development of PUD. However, our experience suggests that this would not fully eliminate the risk.