Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent (TAMA) under investigation for atopic dermatitis (AD) and psoriasis treatment.Phase IIb, double-blind, vehicle-controlled study randomized adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once (QD) or twice daily (BID) for 12 weeks with 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body-surface area (BSA) affected, pruritus numeric rating scale scores, subject impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores.191/247 randomized subjects completed the study. Week-12 IGA responses were higher in tapinarof groups vs vehicle, reaching statistical significance with tapinarof 1%BID; ≥75/90% improvement in EASI from baseline were significantly higher in tapinarof groups (except 0.5%QD and 0.5%BID, respectively); EASI scores were significantly improved in all tapinarof groups; BSA affected was significantly reduced in tapinarof groups (except 0.5%BID). More subjects reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups and POEM improvements were observed in all groups. Most adverse events were mild or moderate.Larger prospective studies are required to confirm reported analyses.Tapinarof is a potential important advance in topical medicine development for AD.