Abstract Objectives Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate intake of antioxidants supplements and risk of keratinocytes cancers (KCs). Methods E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) is a prospective cohort of 98,995 French women aged 40–65 years in 1990. Intakes of antioxidants from diet were estimated via a validated food questionnaire in 1993, and antioxidant supplements use through questionnaires in 1995. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and main known skin cancer risk factors. Results Over 1995–2014, 2425 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KCs risk (HR = 1.37, 95% CI = 1.15–1.62), particularly with BCC (HR = 1.40, 95% CI = 1.17–1.69); and between vitamin E supplement use and risk of both BCC (HR = 1.21, 95% CI = 1.03–1.52) and SCC (HR = 1.43, 95% CI = 1.03–1.99). However, while intake of beta-carotene supplement was associated with increased SCC risk (HR = 1.59, 95% CI = 1.00–2.54), there was not associated with BCC risk, although with no heterogeneity across KC types (Pheterogeneity = 0.21). Vitamin C supplement was also not associated with KCs. Conclusions These findings suggest that intake of vitamin A or E supplement was associated with an increased KCs risk in women. Further studies with information on doses and duration of supplements and the ability to examine their underlying mechanisms are needed. Funding Sources This work was supported by the Mutuelle Générale de l'Education Nationale (MGEN); the Gustave Roussy Institute; and the French League against Cancer (LNCC). Yahya Mahamat-Saleh was supported by research scholarships from the Paris Ile-de-France region and the EHESP (French School of Public Health).