Objective Recently, the number of patients receiving Helicobacter pylori eradication treatment has dramatically increased in Japan, although the eradication rate has gradually decreased. Patient characteristics could affect the eradication rate. Our aim in this study was to investigate the association between failed first-line eradication therapy and hay fever. Methods We researched 356 patients who visited a pharmacy adjacent to the Internal Medicine clinic with a prescription for first-line H. pylori eradication treatment and investigated whether the patients had hay fever using a questionnaire. We separated these patients into 2 groups based on the success or failure of eradication according to the clinical data and performed a logistic regression analysis to investigate the influence of hay fever on first-line eradication failure. Results The eradication rate of patients with and without hay fever was 65.6% and 77.7%, respectively. The adjusted odds ratios according to which patients with hay fever would fail eradication therapy gradually lowered with increasing patient age [≤50 years, odds ratio (OR) 6.81, p=0.089; 51-60 years, OR 2.75, p=0.145; 61-70 years, OR 1.60, p=0.391; >70 years, OR 1.02, p=0.979]. A significant relationship was found for all patients (OR 1.88, p=0.047) and the age group ≤70 years (OR 2.31, p=0.024). Conclusion Patients with hay fever have difficulty with first-line eradication, especially younger patients. The existence of clarithromycin-resistant bacteria is suspected, and other factors may also be involved. When a hay fever sufferer receives first-line treatment, eradication might be difficult and other treatment may be required.