Background VYC-12L is a hyaluronic acid filler to improve skin quality. A prospective study showed safety and effectiveness of VYC-12L for improving cheek skin smoothness and fine lines. Objectives To report participant-reported outcomes, subgroup analyses, and physician experience from the prospective study. Methods Adults with moderate-to-severe Allergan Cheek Smoothness Scale (ACSS) scores were randomized 2:1 to VYC-12L or control (no-treatment with optional treatment). Participant assessments included FACE-Q Satisfaction with Skin, FACE-Q Appraisal of Lines, natural look and feel, Global Aesthetic Improvement Scale (GAIS), and safety. Subgroup analyses examined ACSS responder rate (≥ 1-grade improvement from baseline to 1-month). Results FACE-Q Satisfaction with Skin overall mean scores improved from baseline to 1-month post-treatment by 32.0 and 1.4 in VYC-12L and control, respectively. FACE-Q Appraisal of Fine Lines overall mean scores improved from baseline to 1-month post-treatment by 23.3 and 0.4 in VYC-12L and control, respectively. Treated participants had high median scores (≥ 9.0) of natural look and feel of their cheek skin. GAIS responder rate was high at month 1 (85.5%; 95% CI, 79.3%-91.7%) and through month 6 (83.1%; 95% CI, 76.5%-89.7%). Mean participant-rated pain scores were low (< 3). The most common ISRs were redness, swelling, and lumps/bumps; most resolved within 3 days. Subgroup analyses showed significant differences in ACSS responder rate between VYC-12L and control 1-month post-treatment. Physician injectors reported that VYC-12L was easily injected at the superficial skin and integrated quickly. Conclusions VYC-12L treatment produced significant improvements in satisfaction with skin and cheek skin smoothness, as measured by participant-reported outcome measures.