Keratosis pilaris (KP) is a benign dermatosis consisting of folliculocentric keratotic papules or pustules with surrounding erythema, often on proximal extensor surfaces of extremities. Management strategies for KP largely center on moisturization and exfoliation. Urea, a well-established ingredient in topical skincare, is a component of the natural moisturizing factors with concentration-dependent humectant, emollient, and exfoliative properties. Given the overlap of urea’s properties and management goals of KP, a 4-week, open-label, noncomparative clinical study was conducted to evaluate a moisturizing cream formulated with 20% urea for use in KP. Thirty participants aged 18 to 65 years with KP completed this study. After a 5-day washout period, study participants applied a 20% urea cream once daily to areas of KP for 4 weeks. At baseline, 1-week, and 4-week visits, clinical grading of skin texture, adverse event monitoring, and participant satisfaction questionnaires were conducted. After 1 week and 4 weeks of product use, the percent change in skin smoothness/texture from baseline was significant (P≤0.001). Furthermore, after 4 weeks of use, the majority of participants indicated satisfaction with the feel of their skin, as well as improved confidence and decreased embarrassment related to their skin. No significant adverse events were reported. Overall, the results of this study support that 20% urea cream is generally well tolerated and suitable for use in treating KP. J Drugs Dermatol. 2024;23(1):1274-1277. doi:10.36849/JDD.7806.