BACKGROUND: Oral isotretinoin (Iso) is one of the most commonly used drugs for patients with moderate-to-severe acne; however, its use has been associated with several adverse effects. Some studies have suggested an association between Iso therapy and homocysteine (Hcy), folic acid, and vitamin B12 plasma levels. OBJECTIVE: To evaluate the changes in plasma Hcy, folic acid, and vitamin B12 levels during Iso therapy for acne using meta-analytic methods. METHODS: Five scientific databases (MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science) were searched according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines up to December 2018. A review of 734 publications identified 10 studies that assessed plasma levels of Hcy, folic acid, and vitamin B12 during Iso therapy in acne patients. RESULTS: A total of 10 studies consisting of 592 patients were included in the meta-analysis. Plasma Hcy levels were significantly increased after Iso therapy (weighted mean difference [WMD]: 2.99, 95% confidence interval [CI]: 1.78-4.20, I(2)  = 86%), whereas folic acid levels were significantly decreased after Iso therapy (WMD: -1.03, 95% CI: -1.90 to -0.17, I(2)  = 89%). CONCLUSIONS: This meta-analysis found that Iso therapy was associated with changes in plasma levels of Hcy and folic acid in acne patients. However, further evaluation in controlled studies is needed to verify these results.