BACKGROUND & AIMS: In patients with gastroesophageal reflux disease (GERD) and excessive belching, most belches are supragastric, and can induce reflux episodes and worsen GERD. Supragastric belching (SGB) might be reduced with diaphragmatic breathing exercises. We investigated whether diaphragmatic breathing therapy is effective in reducing belching and proton pump inhibitor (PPI)-refractory gastroesophageal reflux symptoms. METHODS: We performed a prospective study of 36 consecutive patients with GERD refractory to PPI therapy and a belching visual analogue scale (VAS) score of 6 or more, seen at a gastroenterology clinic at a tertiary hospital in Singapore from April 2015 through October 2016. Patients underwent high-resolution manometry and 24-hour pH-impedance studies while they were off PPIs. Fifteen patients were placed on a standardized diaphragmatic breathing exercise protocol (treatment group) and completed questionnaires at baseline, after diaphragmatic breathing therapy, and 4 months after the therapy ended. Twenty-one patients were placed on a waitlist (control subjects), completed the same questionnaires with an additional questionnaire after their waitlist period, and eventually received diaphragmatic breathing therapy. The primary outcome was reduction in belching VAS by 50% or more after treatment. Secondary outcomes included GERD symptoms (evaluated using the reflux disease questionnaire) and quality of life (QoL) scores, determined from the Reflux-Qual Short Form and EuroQoL-VAS. RESULTS: Nine of the 15 patients in the treatment group (60%) and none of the 21 control subjects achieved the primary outcome (P < .001). In the treatment group, the mean belching VAS score decreased from 7.1 ± 1.5 at baseline to 3.5 ± 2.0 after diaphragmatic breathing therapy; in the control group, the mean VAS score was 7.6 ± 1.1 at baseline and 7.4 ± 1.3 after the waitlist period. Eighty percent of patients in the treatment group significantly reduced belching frequency compared with 19% in control subjects (P = .001). Treatment significantly reduced symptoms of GERD (the mean reflux disease questionnaire score decreased by 12.2 in the treatment group and 3.1 in the control group; P = .01). The treatment significantly increased QoL scores (the mean Reflux-Qual Short Form score increased by 15.4 in the treatment group and 5.2 in the control group; P = .04) and mean EuroQoL-VAS scores (15.7 increase in treatment group and 2.4 decrease in the control group). These changes were sustained at 4 months after treatment. In the end, 20 of the 36 patients who received diaphragmatic breathing therapy (55.6%), all with excessive SGB, achieved the primary outcome. CONCLUSIONS: In a prospective study, we found a standardized protocol for diaphragmatic breathing to reduce belching and PPI-refractory gastroesophageal reflux symptoms, and increase QoL in patients with PPI-refractory GERD with belching-especially those with excessive SGB.