PURPOSE: Potassium-competitive acid blockers (P-CABs) are a newer class of acid suppressants with convenient dosing and a rapid onset of action, while showing efficacy comparable to proton pump inhibitors (PPIs) in treating peptic symptoms of gastroesophageal reflux disease (GERD). This study aimed to assess the effect of P-CABs on GERD-related chronic cough. METHODS: This randomized, double-blind, active-controlled, exploratory trial evaluated adults with chronic cough (≥ 8 weeks) and a recent physician diagnosis of GERD or peptic symptoms (< 1 month). Participants were randomized (1:1) to receive either fexuprazan 40 mg or esomeprazole 40 mg (PPI) once daily for eight weeks, along with matched placebos. The primary endpoint was the change in Leicester Cough Questionnaire (LCQ) score from baseline. Secondary endpoints included changes in the cough severity Numerical Rating Scale (NRS) and Reflux Disease Questionnaire (RDQ) scores. Safety was evaluated through monitoring adverse events. RESULTS: Of the 190 subjects recruited, 161 met the selection criteria and were randomized, and 146 completed the trial. The participants were predominantly female (74.3%, mean age 39 ± 12 years). After 8 weeks of treatment, cough-related quality of life improved significantly, with comparable LCQ scores change between the groups (fexuprazan: 4.9 ± 4.0 vs. esomeprazole: 5.3 ± 3.8, p = 0.558). Changes in cough severity NRS and RDQ scores were also similar between the groups. Adverse events were comparable and consisted mostly of mild symptoms. CONCLUSION: These findings support the potential of P-CABs as a promising alternative to PPIs for patients with chronic cough requiring acid-suppressive therapy.