Hand dermatitis is a multifactorial skin disorder in which skin barrier impairment is involved in the pathogenesis. The development of topical agents that improve skin barrier function is therefore a promising approach for the management of hand dermatitis. Topically applied lipids may interfere with skin barrier function, and emollients containing skin-related lipids have been suggested to facilitate repair of the skin barrier. However, evidence for the superiority of emollients containing skin-related lipids over the more traditional emollients is still lacking. The aim of this study was to compare an emollient containing skin-related lipids (Locobase Repair) with a traditional petrolatum-based emollient for the management of hand dermatitis. Adult males and females (n = 30) with mild to moderate chronic hand dermatitis were treated twice daily for 2 months either with an emollient containing skin-related lipids or with a pet.-based emollient. In the case of exacerbation, the patients of both treatment groups were allowed to use a mild corticosteroid according to instructions. Both treatment regimes significantly improved clinical signs of hand dermatitis as assessed by the investigator global assessment, hand eczema area and severity score. We did not observe significant differences in the improvement of clinical signs, itching, patients' assessment of efficacy, cosmetic acceptability or usage of topical corticosteroids between both treatment groups. In conclusion, this study confirms that the frequent use of emollients may be useful in the therapy of hand dermatitis. However, we could not demonstrate the superiority of this particular emollient containing skin-related lipids in patients with chronic hand dermatitis.