Introduction <p>Multimodal topical therapy is recommended by the American Academy of Dermatology for the treatment of acne vulgaris. However, no data are available regarding stability of clascoterone cream 1% when combined with other topical acne medications. The purpose of this study was to evaluate the stability of clascoterone in the presence of tretinoin, adapalene, dapsone, azelaic acid, benzoyl peroxide (BP)/clindamycin, BP/adapalene, and encapsulated BP.</p> Methods <p>Clascoterone cream (0.5&#xa0;mL) was layered over 0.5&#xa0;mL of each of the other products on an individual microscope slide and incubated for 8&#xa0;h at 37&#xa0;°C. Material from the slides was extracted in methanol and tetrahydrofuran for high-pressure liquid chromatography mass spectrometry (1&#xa0;mL/min flow rate; 30&#xa0;°C). Combinations of clascoterone with tretinoin and adapalene were reinjected 12&#xa0;h after the initial injections to confirm consistent clascoterone detection. Percent recovery of clascoterone for each combination was calculated from a standard curve serially diluted in methanol.</p> Results <p>The mean percentage of clascoterone recovered after incubation with other drugs ranged from 98% to 119%, with 86% recovered following injection of clascoterone alone. Reinjected clascoterone-tretinoin and clascoterone-adapalene samples yielded clascoterone recovery percentages of 97% and 93%, respectively, both within 8% of those recovered from the initial injections.</p> Conclusions <p>Clascoterone demonstrated consistent and reproducible stability in the presence of other topical acne medications.</p>