The objective of this 6-week clinical study was to demonstrate the effectiveness of a natural ingredient-based moisturizing cream versus a colloidal oatmeal moisturizing cream in improving the hydration, barrier function, appearance, and feel of dry leg skin. Thirty-two subjects completed the study. After a 5-day washout, subjects used the natural ingredient-based moisturizing cream and oatmeal-containing cream on randomly-assigned legs twice a day for a period of three weeks. For the following two weeks subjects did not use any moisturizer on their legs. Skin moisture measurements showed a statistically significant increase in hydration for both products at all time points during the treatment phase of the study. Both products reduced transepidermal water loss measurements during the treatment phase of the study, showing their abilities to improve stratum corneum barrier function. Clinical evaluations showed that both products significantly decreased visual dryness and tactile roughness during the treatment phase. Improvements in the assessed clinical parameters persisted even after treatment cessation. In conclusion, the natural ingredient-based moisturizing cream was highly effective in providing moisturization and improving the skin barrier of subjects with very dry leg skin. It also produced significant improvements in visual dryness and tactile roughness that persisted during regression. Overall, these results show that the natural ingredient-based moisturizing cream delivers comparable benefits to that of a colloidal oatmeal-containing benchmark product and is an option for health care providers and consumers who seek relief from dry skin and prefer a product with all-natural ingredients. J Drugs Dermatol. 2018;17(7):758-764.