Atopic dermatitis (AD), a chronic inflammatory skin disease, is typically treated with topical corticosteroids in patients with mild to moderate disease, creating an ongoing need for nonsteroidal therapies. As part of a phase 2, randomized, dose-ranging study of ruxolitinib (Janus kinase [JAK]1/JAK2 inhibitor) cream, twice-daily 1.5% ruxolitinib cream was compared with twice-daily 0.1% triamcinolone cream (midpotency topical corticosteroid) in adults with mild to moderate AD for ≥2 years. Triamcinolone cream was only used for 4 continuous weeks of the 8-week vehicle-controlled period for safety considerations; thus, data here are reported up to week 4 in the study. At week 4, substantially more patients who applied 1.5% ruxolitinib cream vs 0.1% triamcinolone cream achieved ≥75% or ≥90% improvement from baseline in the Eczema Area and Severity Index (56.0% vs 47.1% and 26.0% vs 13.7%, respectively) and Investigator’s Global Assessment Score of 0/1 with ≥2-grade improvement from baseline (38.0% vs 25.5%). Significantly more patients achieved ≥2-point improvement in itch numerical rating scale (NRS) on day 2 with 1.5% ruxolitinib cream vs 0.1% triamcinolone cream (42.5% vs 20.5% [P=0.0412]), and significantly more patients achieved ≥4-point improvement in itch NRS at week 4 (62.5% vs 32.3% [P=0.0128]). Ruxolitinib cream was well tolerated, with no clinically significant application site reactions. Treatment-emergent adverse events were mild/moderate in severity; nasopharyngitis and headache were most common (n=2 [4.0%] each). In summary, ruxolitinib cream is a well-tolerated nonsteroidal therapy with efficacy at least as good as a midpotency topical corticosteroid while avoiding the potential concerns of long-term corticosteroid use.