Peptic ulcer disease (PUD) remains a frequent and clinically significant problem in both primary and acute care settings. Proton pump inhibitors (PPIs) have traditionally served as the cornerstone of therapy. Vonoprazan, a potassium-competitive acid blocker (P-CAB), has gained increasing use due to its rapid and sustained acid suppression, yet its advantages over PPIs in real-world clinical practice remain inadequately defined.To critically appraise recent evidence comparing vonoprazan with PPIs in the management of acute PUD, with a focus on ulcer healing, upper gastrointestinal (GI) rebleeding, adverse events, and cost-effectiveness from a primary care perspective.A structured PubMed search identified 19 eligible studies published between 2019 and 2025, including randomized trials, cohort studies, meta-analyses, and network meta-analyses. Exclusion criteria included non-human studies, non-English publications, inconclusive results, and studies unrelated to peptic or duodenal ulcers. Extracted outcomes included ulcer healing rates, upper GI rebleeding, treatment-related adverse events, hospitalization duration, transfusion needs, and economic evaluations.Across studies, vonoprazan achieved ulcer healing rates that were consistently non-inferior and in some cases modestly superior to PPIs. Several East Asian real-world cohorts reported numerically lower short-term rebleeding rates with vonoprazan, though significance varied. Serious adverse events did not differ between groups, while minor gastrointestinal symptoms appeared slightly more common with vonoprazan but without clinical consequence. Economic analyses suggested potential cost-effectiveness for high-risk subgroups, although higher upfront drug costs limit widespread use. Mortality outcomes were low and showed no meaningful differences.Vonoprazan’s potent acid suppression may offer clinical benefits in selected scenarios, particularly when rapid control is required or PPI response is suboptimal. However, the concentration of available evidence in East Asia and heterogeneity across studies limit broader generalization. For primary care physicians, treatment selection must balance clinical efficacy with medication cost, patient comorbidity, and local practice patterns.Vonoprazan offers potent and reliable acid suppression with efficacy and safety comparable to PPIs in acute PUD management. Although cost remains a limiting factor, it represents a reasonable therapeutic option in appropriately selected patients. Treatment choice should remain individualized, guided by clinical risk, treatment response, and healthcare system context.