BACKGROUND: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics. OBJECTIVES: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention. METHODS: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n = 106) to examine effect modification by age, self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, skin hemoglobin, skin hemoglobin saturation, skin coloration, sun exposure, and baseline intake of carotenoids from foods. Skin carotenoid concentrations were assessed using pressure-mediated reflection spectroscopy (Veggie Meter), and plasma carotenoid concentrations were measured using high-performance liquid chromatography. RESULTS: In bivariate analyses, among the high-dose group (8 mg/d), those of older age had lower skin carotenoid responsiveness than their younger counterparts, and those with greater hemoglobin saturation and lighter skin had higher skin carotenoid score responsiveness. In the moderate-dose group (4 mg/d), participants from one site had greater plasma carotenoid responsiveness than those from other sites. In multivariate analyses, participants with higher baseline skin carotenoids had smaller skin carotenoid responses to both moderate and high doses. CONCLUSIONS: Changes in skin carotenoid scores in response to interventions to increase fruit and vegetable intake should be interpreted in the context of baseline skin carotenoid scores, but other variables (e.g., self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, and sun exposure) do not significantly modify the effect of carotenoid intake on changes in skin carotenoid scores. This trial was registered at clinicaltrials.gov as NCT04056624.