A double-blind, randomized, split-face, comparative 12-day facial tolerance study was conducted in 30 female subjects with sensitive skin between a new 10% sodium sulfacetamide & 5% sulfur aqueous gel in a 10% urea vehicle (product A) and a 10% sodium sulfacetamide & 5% sulfur topical suspension (product B). These sensitive skin subjects had a personal history of signs of irritation from soaps, acne medications and other facial products or required discontinuation or modification of topical retinoid usage in facial tolerance protocols. 14 subjects had diagnosed rosacea and 16 had diagnosed acne. All subjects used each test product once a day (PM) applying a pea-sized amount to the designated side of the face. 28 subjects completed the study. Subjects were visually evaluated by an expert grader for erythema and dryness (0–8 scale) initially and on days 4, 9 and 12. In addition, instrumental evaluation measured skin erythema (Minolta chromameter) and transepidermal water loss (TEWL). For the expert grader results, in the acne group, product A (with urea) showed a statistically significant, progressive increase in the number of patients with favorable response for both dryness and erythema vs. a progressively worsening result for product B. This was also reflected in the instrumental data where product A (with urea) showed statistically significant, lower (favorable) scores vs. product B (without urea) for TEWL and redness. In the rosacea subjects, no significant differences were seen between the two products, although product A (with urea) tended to have lower (favorable) TEWL and redness scores. The progressively increasing water loss from the product B (without urea) treated acne subjects, indicates a disruption of the skin’s barrier function. The main difference between the two products is the presence of 10% urea in product A; we therefore attribute the statistically significant benefits (for both dryness and erythema) from the use of product A to urea.