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Aim of this systematic review was to assess the effects of orthopedic treatment for Class II malocclusion with Functional Appliances (FAs) on the dimensions of the upper airways. Eight databases were searched up to October 2020 for randomized or nonrandomized clinical studies on FA treatment of Class II patients with untreated control groups. After duplicate study selection, data extraction, and risk of bias assessment according to Cochrane guidelines, random effects meta-analyses of mean differences (MDs) and their 95% confidence intervals (CIs) were performed, followed by subgroup/meta-regression analyses and assessment of the quality of evidence. A total of 20 nonrandomized clinical studies (4 prospective/16 retrospective) including 969 patients (47.9% male; mean age 10.9 years) were identified. Orthopedic treatment with FAs was associated with increased oropharynx volume (MD = 2356.14 mm3; 95% CI = 1276.36 to 3435.92 mm3; p < 0.001) compared to natural growth. Additionally, significant increases in nasopharynx volume, minimal constricted axial area of pharyngeal airway, and airway were seen, while removable FAs showed considerably greater effects than fixed FAs (p = 0.04). Finally, patient age and treatment duration had a significant influence in the effect of FAs on airways, as had baseline matching and sample size adequacy. Clinical evidence on orthopedic Class II treatment with FAs is associated with increased upper airway dimensions. However, the quality of evidence is very low due to methodological issues of existing studies, while the clinical relevance of increases in airway dimensions remains unclear.