CONTEXT: Gastroesophageal reflux disease (GERD) is a chronic condition that affects a growing number of people and is currently among the most common disorders seen in clinical practice. OBJECTIVE: To develop a protocol for the management of GERD with osteopathic manipulative therapy (OMTh) applied to the diaphragm and esophagus, and to evaluate the protocol’s effectiveness using the quality of life scale (QS-GERD) for the disease. METHODS: In this single-blinded prospective study, an OMTh protocol focusing on the diaphragm and esophagus was applied to a single patient, who had received a diagnosis of GERD 4 years previously. Outcomes were measured using the QS-GERD, which has a total possible score ranging from 0 to 45 (the lower the score, the better the quality of life) and a level of satisfaction from very satisfied to incapacitated. The OMTh protocol was applied at 3 sessions (initial session, second session 1 week after the first, and third session 2 weeks after the second), and the patient completed the QS-GERD 4 times (before the first session, before the third session, and 2 and 4 weeks after the third session). RESULTS: The OMTh protocol was administered without adverse events, and the patient reported positive outcomes after the third session. The QS-GERD showed a score improvement from 13 of 45 to 4 of 45. CONCLUSION: The results in the present report show that OMTh applied to the diaphragm and esophagus may improve symptoms of GERD and should be added to the somatovisceral approach to the care of patients with this condition.