This prospective Canadian pilot study assesses the platelet response rate in H. pylori positive and negative patients and evaluates potential mechanisms to explain response. Patients with ITP received H. pylori eradication therapy and platelet counts at day 56 were used to assess response. Gastric permeability, stool H. pylori antigen and serum CagA anti-body were done at baseline and at day 60. Twenty-two patients were enrolled with an overall response rate of 27% (6/22). The prevalence of H. pylori was 18% (4/22). Seventy-five percent of the H. pylori positive patients (3/4) achieved a response compared to 17% (3/18) of the H. pylori negative patients (P < 0.05). Seventy-five percent of complete responders have demonstrated long-term ongoing responses at 48 months of follow-up. A trend towards lower post-eradication gastric permeability in responders was seen. Although the prevalence of H. pylori is low, H. pylori positive Canadian patients with ITP may benefit from a trial of H. pylori eradication therapy as a safe and effective means to achieve long term platelet response.