The effects of vonoprazan, a new potassium-competitive acid blocker, on gastroesophageal reflux disease (GERD) symptom are not fully elucidated. The aim of this study is to determine the effect of vonoprazan on GERD and associated gastrointestinal symptoms. We retrospectively reviewed 88 Helicobacter pylori negative patients with GERD treated with vonoprazan 10 mg daily. Symptoms were evaluated using the Izumo scale, which reflects quality of life related to various abdominal symptoms. The rates of improvement and resolution of GERD symptoms were 86% (76/88) and 57% (50/88), respectively. Improvement and resolution in patients with erosive esophagitis was higher than in those with non-erosive reflux disease (91% vs 83%, p = 0.260 and 71% vs 47%, p = 0.025, respectively). We attempted to identify factors which predict the effects of vonoprazan. Multivariate analysis identified advanced age (≥60-year-old) (odds ratio [OR] 7.281, 95% confidence interval [CI] 2.056-25.776, p = 0.002), obesity (BMI ≥ 24) (OR 3.342, 95%CI 1.124-9.940, p = 0.030) and erosive esophagitis (OR 4.368, 95%CI 1.281-14.895, p = 0.018) as positive predictors of resolution of GERD symptoms. Alcohol use (OR 0.131, 95%CI 0.027-0.632, p = 0.011) and history of H. pylori eradication (OR 0.171, 95%CI 0.041-0.718, p = 0.015) were identified as negative predictors. Vonoprazan also improved epigastric pain (73%), postprandial distress (60%), constipation (58%) and diarrhea (52%) in patients with GERD. In conclusion, vonoprazan 10 mg daily is effective in improving GERD symptoms. Advanced age, obesity, erosive esophagitis, alcohol use and history of H. pylori eradication influence the resolution of GERD symptoms. Treatment with vonoprazan favorably affects gastrointestinal symptoms in patients with GERD.