AbstractBackgroundFood allergies pose a global healthcare challenge, underscoring the need for effective interventions. This study evaluated the efficacy and safety of epicutaneous immunotherapy (EPIT) for food allergen desensitisation.MethodsWe conducted a systematic review of randomised controlled trials by searching Ovid EMBASE, PubMed and Scopus in April 2024. Using a random‐effects meta‐analysis, we evaluated the clinical effectiveness and harms of EPIT, reporting results as risk ratios with 95% confidence intervals (CI).ResultsAfter screening 460 abstracts and 35 full reports, 11 were included: nine on peanuts and two on cow's milk (CM). Peanut EPIT had a 51.2% treatment response versus 22.4% for placebo (RR 2.16, CI 1.49–3.12; four studies; moderate certainty). The RR for milk EPIT response rate was 1.78 (CI 1.06–3.00; one study). Five peanut studies (1396 patients) reported EPIT‐related adverse events (RR 1.39, CI 0.94–2.05; low certainty).ConclusionsEPIT offers a moderate treatment response with a favourable safety profile and significant improvements in quality of life. Current knowledge of EPIT remains limited, with evidence confined to peanut and CM allergies. There is a lack of research on sustained unresponsiveness achieved through food EPIT.