Background <p>Androgenetic alopecia (AGA), the most common cause of hair loss, leads to significant psychological and cosmetic concerns in males and females both. Minoxidil is a widely used standard therapy for treating AGA, while Platelet-rich plasma (PRP), a new emerging treatment, has also gained popularity. However, there are no data comparing the efficacy of both treatment options to guide clinical decision-making. This systematic review and meta-analysis aims to compare and evaluate the effectiveness and safety profiles of PRP versus topical minoxidil for the treatment of AGA.</p> Methods <p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to conduct a systematic review. Databases including Scopus, Cochrane, Science Direct, Google Scholar, Embase, and PubMed were searched from inception to July 2024. We included randomized controlled trials (RCTs) that compared PRP and topical minoxidil, enrolling both men and women diagnosed with AGA with no age restriction. Non-RCTs, letters, retrospective studies, guidelines, review papers, editorials and commentaries were excluded. Cochrane risk-of-bias tool was used to assess the quality of the studies. Data were pooled using a random effect model.</p> Results <p>A total of 789 articles were screened, and nine RCTs with 451 participants were included in the meta-analysis. Upon comparing the treatment outcomes, PRP and minoxidil showed no significant difference in hair density (odds ratio [OR]: 9.09; confidence interval [CI]: 6.73, 24.91). Patient satisfaction was significantly higher for those receiving PRP therapy than 5% minoxidil (OR: 2.77; CI: 1.53,5.04). Negative hair pull test results significantly favored PRP over minoxidil (82.75% vs. 52.94%, respectively). However, outcomes for moderate to high regrowth and terminal hair count were similar between the two treatments.</p> Conclusion <p>While PRP therapy shows promise and has produced better patient outcomes than minoxidil, this meta-analysis does not demonstrate a clear advantage of PRP over minoxidil in key clinical outcomes such as hair density, mean terminal hair count, or moderate-to-high regrowth. The high heterogeneity across studies emphasizes the need for larger, standardized trials to establish definitive conclusions.</p> Level of Evidence I <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="http://www.springer.com/00266">www.springer.com/00266</a>.</p> <p><b>Prospero registration</b>: (CRD42024570523)</p>