Refractory hypothyroidism has been increasingly identified worldwide. Primary hypothyroidism is considered refractory when there is a persistent elevation of thyroid-stimulating hormone (TSH) above the upper limit of normal despite escalating doses of levothyroxine with or without the persistence of hypothyroid symptoms. Further escalation of levothyroxine to supratherapeutic doses could be associated with potential complications such as iatrogenic hyperthyroidism, cardiac failure, and other conditions. Therefore, physicians should rule out non-compliance and pursue a further evaluation to identify etiologies for increased requirements or decreased absorption of levothyroxine in patients not achieving therapeutic doses. Here, we present a 40-year-old Indian male with worsening refractory hypothyroidism that resolved following eradication of his Helicobacter pylori ( H. pylori ) infection. Herein, we highlight a unique and reversible cause of refractory hypothyroidism. With this case report, we hope to encourage physicians to include H. pylori testing in the evaluation of primary hypothyroidism refractory to treatment.