Background:In gastroesophageal reflux disease (GERD), opposite to traditional medications which do not target the pathophysiological mechanism of GERD, manual diaphragmatic activation maneuver (MDAM) directly corrects the pathophysiological mechanism of GERD, as it strengthens/augments the anti-reflux barrier. Purpose: This study aimed to investigate the effect of MDAM on GERD patients' diaphragmatic excursion (DE), diaphragmatic thickness fraction (DTF), and 19-item Pittsburgh sleep quality index (PSQI). Methods: Thirty GERD sufferers were randomly assigned into two 15-patient groups, the MDAM group (study group) and the control group. Both GERD groups received for-GERD-designed medical routine/care for 2 months. A 30-minute manual diaphragmatic activation maneuver was applied to the MDAM group only three times per week for 2 months. For all GERD patients in both groups, DE, DTF, and PSQI were the outcomes of this randomized GERD trial. Results: All outcomes (DE, DTF, and PSQI) of this GERD trial significantly improved in both GERD groups. The percent of change in GERD patients' DE, DTF, and PSQI of the MDAM group was 8.65, 19.56, and 60.40%, respectively, and that in the GERD group that received only GERD routine medical care was 2.43, 5.80, and 34.82%, respectively. Conclusions: manual diaphragmatic activation maneuvers improve GERD in DE, DTF, and PSQI more than the other group who received only traditional medical care.