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Background Aim. To compare the efficacy of omeprazole to other proton-pump inhibitors (PPIs) or placebo for the treatment of acid peptic disorders (APDs) using a comprehensive literature search including hard-to-access journals and non-English articles. Methods. PubMed, Google Scholar, and China National Knowledge Infrastructure were searched (from inception to March 2023) for trials comparing omeprazole to other types of PPIs or placebo for the treatment APD. Efficacy was analyzed separately for erosive diseases and nonerosive diseases. Primary outcomes included improvement of APD symptoms and frequency of ulcer or erosion healing. Secondary outcomes included adverse events, cost effectiveness, nocturnal acid breakthrough, and length of stay if hospitalized. Random and fixed-effects models were used to determine estimates of efficacy. Results. Thirty-one eligible trials (N = 10,539 participants) were analyzed, including 12 articles not typically included in previous reviews due to translation or journal access issues. Omeprazole significantly improved heartburn compared to placebo (RR = 2.47, 95% CI: 2.13 and 2.86, and p |