Introduction: Cardiovascular adverse effects of COX-2 inhibitors are well described. Nevertheless, no study explored the cutaneous and vascular adverse effects of COX-2 inhibitors [1]. The aim of this study is to identify and quantify the risk of skin ulcer associated with COX-2 inhibitors in real world setting. Material and methods: A population-based nested case control study was conducted from a representative sample of the French nationwide claims database, “EGB,” for the 2012–2016 period [2]. Cases were defined as patients who had consumed at least two boxes of wound dressing during 1 month between 2012 and 2016. The index date was the date of first period of reimbursement of wound dressing for skin ulcer. Up to four potential controls were selected for each case among subjects free from skin ulcers. Conditional logistic models were used to estimate adjusted odds ratios (aORs) and their 95% CIs. Cumulative exposure of drug class was considered using quartile as a categorical variable. The status of exposure was defined using a categorical variable. Results: For diabetes foot ulcers, pressure ulcers, and vascular ulcers, respectively 19,982, 4,584, and 41,632 cases fulfilled the inclusion criteria. Among cases and controls, an increased risk of all types of ulcers was found for a cumulative exposure to COX-2 inhibitors exceeding 90 days with aOR = 1.35 (95% CI 1.03–1.77) for diabetic foot ulcer, aOR = 2.04 (95% CI 1.63–2.56) for pressure ulcers, and aOR = 1.89 (95% CI 1.71–2.11) for vascular ulcers. Current exposure was associated with a higher risk of skin ulcer with aOR = 1.63 (95% CI 1.06–2.49) for diabetic foot ulcer, aOR = 2.20 (95% CI 1.52–3.19) for pressure ulcers, and aOR = 3.0 (95% CI 2.57–3.52) for vascular ulcers. Discussion/Conclusion: Our results suggest that COX-2 inhibitors are associated with a dose and time-dependent risk of skin ulcers. Given the observational nature of this study, we cannot exclude unmeasured and residual confounding.< Réduire