Purpose <p>This narrative review evaluates the clinical value of key globally marketed potassium-competitive acid blockers (P-CABs) for acid-related diseases (ARDs) based on current evidence-based medical research to inform clinical practice.</p> Methods <p>We compare P-CABs and proton pump inhibitors (PPIs) in terms of their mechanisms of acid suppression, speed of onset, metabolic pathways, and long-term safety. We present a detailed comparison of the clinical efficacy of individual P-CABs and PPIs for gastroesophageal reflux disease (GERD), peptic ulcers, and <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication, synthesizing findings from recent clinical trials and meta-analyses.</p> Results <p>This highlights the advantages of P-CABs, such as rapid acid control and the achievement of maximal efficacy with the first dose, as well as their reduced susceptibility to CYP2C19 polymorphisms. Evidence suggests that P-CABs have potential advantages in the initial and maintenance treatment of erosive esophagitis (EE). P-CABs demonstrate non-inferiority to PPIs in ulcer healing. For <i>H. pylori</i> eradication, P-CABs are comparable to PPIs in standard regimens; however, P-CAB-based dual therapy (e.g., P-CAB + high-dose amoxicillin) is emerging as a promising first-line treatment option.</p> Conclusion <p>This review emphasizes the evolving role of P-CABs in optimizing management strategies for ARDs.</p>