Abstract Vitiligo is a chronic inflammatory autoimmune disease that targets melanocytes, causing skin de-pigmentation. A cream formulation of the Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib demonstrated substantial re-pigmentation in a phase 2 study in adults with vitiligo. In two multinational, randomized, double-blind, vehicle-controlled phase 3 studies of adults and adolescents with vitiligo (TRuE-V1, NCT04052425; TRuE-V2, NCT04057573), ruxolitinib cream was superior to vehicle at Week 24 in the primary and all key secondary endpoints. Pooled results on achievement of ≥ 50% improvement in the Vitiligo Area Scoring Index (VASI50) by body region in TRuE-V1/TRuE-V2 were analysed and are reported herein. Patients ≥ 12 years old with nonsegmental vitiligo (NSV) with de-pigmentation covering ≤ 10% total body surface area, including a total VASI (T-VASI) score ≥ 3, were eligible for enrolment. Patients were randomized 2 : 1 to twice-daily 1·5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply twice-daily 1·5% ruxolitinib cream through Week 52 (open-label extension). The percentage of patients achieving VASI50 was calculated for each body region [head and neck (not including face), hands, upper extremities, trunk (including genitals), lower extremities, feet] and total body (excluding face). In total, 674 patients were randomized in the TRuE-V studies (ruxolitinib cream, n = 450; vehicle, n = 224); 661 patients were included in the efficacy analysis (1 site excluded for data quality) and 569 continued in the open-label extension (ruxolitinib cream from Day 1, n = 385; crossover from vehicle, n = 184). At Week 12, more patients who applied 1·5% ruxolitinib cream vs. vehicle achieved VASI50 in the head and neck (28·3% vs. 19·8%), upper extremities (14·1% vs. 11·0%), trunk (15·5% vs. 12·9%) and lower extremities (15·1% vs. 10·9%). At Week 24, more patients who applied 1·5% ruxolitinib cream vs. vehicle achieved VASI50 regardless of body region [head and neck, 45·3% vs. 23·8%; hands, 24·9% vs. 14·4%; upper extremities, 33·2% vs. 8·2%; trunk, 26·4% vs. 12·3%; lower extremities, 29·5% vs. 12·2%; feet, 18·5% vs. 12·5%; total body (excluding face), 20·8% vs. 6·9%]. Similarly at Week 52 more patients who applied ruxolitinib cream from Day 1 achieved VASI50 than those who switched over from vehicle after Week 24 (head and neck, 68·1% vs. 51·0%; hands, 38·2% vs. 29·2%; upper extremities, 56·7% vs. 34·9%; trunk, 48·4% vs. 25·4%; lower extremities, 54·5% vs. 32·3%; feet, 29·3% vs. 22·5%; total body [excluding face], 47·7% vs. 23·3%). Attainment of VASI50 at Week 52 among crossover patients (i.e. after 28 weeks of ruxolitinib cream) was consistent with Week 24 data in patients who applied ruxolitinib cream from Day 1. Adolescents and adults with NSV applying ruxolitinib cream achieved VASI50 in higher percentages compared with vehicle at Week 12 in the head and neck, upper extremities, trunk and lower extremities and at Week 24, regardless of the body region involved. The percentage of patients who achieved VASI50 increased through Week 52, including among patients who switched over from vehicle to ruxolitinib cream after Week 24. In summary, ruxolitinib cream produced a clinically meaningful re-pigmentation of all body regions (including hands and feet that are notoriously difficult to re-pigment) in TRuE-V1/TruE-V2 through Week 52, including among patients who switched over to ruxolitinib cream from vehicle after Week 24.