<p>Key features of lip aging include loss of volume, color, and definition as well as increases in lines/wrinkles and uneven skin texture. A single-center, open-label clinical study was conducted to assess the efficacy and tolerability of a novel, topical two-step lip treatment (HA5 LS) in female subjects presenting with mild to moderate lip dryness and mild to severe lip condition. Subjects were instructed to apply HA5 LS at least three times a day to ensure coverage 8 hours a day for four weeks. Clinical assessments for efficacy and tolerability were conducted at baseline, baseline post-application, week 2, and week 4. Standardized digital photography, subject self-assessment questionnaires, and instrumentation measurements for skin hydration (corneometer) and lip plumpness (digital caliper) were also conducted. Thirty-six female subjects aged 22-40 years enrolled in the study. HA5 LS provided instant and long term effects, achieving significant improvements in all clinical grading parameters including lip texture, color, definition/contour, scaling, cupping, lines/wrinkles, lip plumpness, and overall lip condition from baseline post-application to week 4 (all P less than equal to .001; Wilcoxon signed-rank test). Instrumentation measurements for hydration and digital caliper at weeks 2 and 4 were also significant (all P less than equal to .032; paired t-test). HA5 LS was also well-tolerated and highly-rated by subjects throughout the study duration. Results from this study suggest that HA5 LS addresses the key features of lip aging, providing both instant and long-term benefits.</p> <p><em>J Drugs Dermatol. 2017;16(4):366-371.</em></p>.