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Regarding ethical considerations of randomized controlled trials (RCTs) in children, limited evidence for mild hand, foot, and mouth disease (HFMD) is available. Recently, with the increasing but result-conflicting RCTs published around herbal granules of heat-clearing and detoxifying (HGs-HD), a head-to-head comparison is urgently needed to choose a suitable therapy for clinical practice. This study was conducted according to the preferred reporting items for systematic review and meta-analysis (PRISMA) extension statement for network