Approved topical treatments for seborrheic keratoses (SKs) are an unmet need.To evaluate the safety and efficacy of 40% hydrogen peroxide topical solution (HP40) versus vehicle for the treatment of SKs (A-101-SEBK).A total of 937 patients with 4 SKs each (≥1 lesion each on the face and on the trunk and/or an extremity) were randomized 1:1 to HP40 or vehicle. At each visit, SKs were graded using the Physician's Lesion Assessment (PLA) scale (0, clear; 1, nearly clear; 2, ≤1 mm thick; and 3,1 mm thick). After 1 treatment, SKs with a PLA score higher than 0 were re-treated 3 weeks later.At day 106, significantly more patients treated with HP40 than with vehicle achieved a PLA score of 0 on all 4 SKs (study 1, 4% vs 0%; study 2, 8% vs 0% [both P .01]) and on 3 of 4 SKs (study 1, 13% vs 0%; study 2, 23% vs 0% [both P .0001]). A higher mean per-patient percentage of SKs were clear (study 1, 25% vs 2%; study 2, 34% vs 1%) and clear or nearly clear (study 1, 47% vs 10%; study 2, 54% vs 5%) with HP40 than with vehicle. Local skin reactions were largely mild and resolved by day 106.The optimal number of treatment sessions was not evaluated.Application of HP40 was well tolerated and effective in the removal of SKs.