Background and rationale: Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. Helicobacter pylori (H. pylori) infection has been associated with an increased risk of thyroid diseases (TDs) and it may cause some sort of mal absorption to thyroxine replacement therapy causing a treatment refractory state. Aim of work: The aim of the work is to estimate the prevalence of H. pylori in hypothyroid patients and its relation to unresponsiveness to treatment. Patients and method: We analyzed 211 hypothyroid patient on treatment. We estimate stool antigen for H. pylori and correlate it with other parameters in hypothyroid patients. Results:  Two hundred and eleven (211) patients were included in this study, of these, 101/211 (47.9%) were euthyroid on treatment and 110/211 (52.1%) had refractory hypothyroidism with high dose of LT4. The mean age of patients in our study was 55.67 ± 13.53 years, with 151 (71.6%) female patients.  In the current study, we noticed that prevalence of H. pylori was higher in treatment refractory hypothyroidism than euthyroid patients. Conclusions: This study suggested that there is a significant association between H. pylori infection and treatment-refractory hypothyroidism. And eradication of H. pylori may help in overcoming the issue of resistant to thyroxine therapy.