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Facial erythema is a representative symptom of rosacea patients that greatly impairs quality of life. Recently, the therapeutic effects of intradermal injection of botulinum toxin type-A on erythema have been investigated. Fractional microneedling radiofrequency has been reported to be effective in dermal remodeling and anti-inflammation. To obtain enhanced therapeutic effects with a less painful and easier approach, a treatment regimen using transdermal botulinum toxin delivery with fractional microneedling radiofrequency was developed. We aimed at investigating the efficacy and safety of transdermal botulinum toxin delivery with fractional microneedling radiofrequency in treating the erythema of rosacea. This was a retrospective review of 20 patients with facial erythema associated with rosacea. All patients underwent two sessions of treatment at 4-week intervals. Standardized photographs were taken, and the clinicians' erythema assessment (CEA), erythema index (EI) measured through a spectrophotometer, investigator's global assessment (IGA), and subjective satisfaction and side effects were evaluated at the baseline and 4, 8, and 12 weeks after the baseline. Compared to the baseline, CEA levels significantly decreased after 8 weeks (P = 0.018) and 12 weeks (P = 0.005). As an objective measure, EI was observed to decrease significantly at 4 weeks (P = 0.04) and 8 weeks after the baseline (P = 0.005) compared with the baseline. Ninety-five percent of patients were either very satisfied or satisfied with the treatment. None of the patients experienced remarkable side effects. A novel treatment regimen involving transdermal botulinum toxin delivery and fractional microneedling radiofrequency may be an effective and safe option for reducing the facial erythema of rosacea. [ABSTRACT FROM AUTHOR]