ObjectiveTo systematically review comparative studies of generic versus brand-name drugs published from 2020 to 2025, evaluate their methodological quality, and synthesize high-quality evidence to inform rational clinical use and policy development. MethodsWe searched PubMed, Embase, Cochrane Library, CNKI, VIP, WanFang Data, and CBM databases for studies published between 2020 and 2025. Two reviewers independently screened articles and extracted data. We used appropriate tools to evaluate study quality based on design. We conducted descriptive analyses of study characteristics and synthesized results from high-quality studies. ResultsWe included 125 studies from countries such as China, Russia, and the United States. Most studies used single-center cohort designs (44.0%) with medium (100 to 500 cases, 39.2%) or large samples (500 to 5 000 cases, 30.4%). These studies covered over 90 drugs, mainly in cardiovascular, oncology, and anti-infective fields. We rated 55 studies (44.0%) as high quality. Common issues included limited follow-up, missing sample size estimation, and weak confounding control. Among high-quality studies, about 80% found no major differences in efficacy or safety between generic and brand-name drugs. Some also showed cost advantages for generics. ConclusionResearch comparing generic and brand-name drugs has grown over the past five years. High-quality studies support clinical equivalence and substitution. Future studies should follow more rigorous methods to provide stronger evidence for clinical practice and policymaking.