Introduction: Antidopaminergic antipsychotics have been associated with an increased risk of ischemic stroke. So far, this risk has not been assessed for antidopaminergic antiemetics (ADAs). This study aimed at estimating the risk of ischemic stroke associated with ADA use. Material and methods: Case-time-control study, based on data from the French reimbursement healthcare system (SNDS). Participants: Patients ≥18y with a first ischemic stroke between 2012 and 2016, and at least one ADA reimbursement in the 70 days before stroke. ADA use was self-compared between a risk-period (days [−14, −1] before stroke) and 3 reference periods (days [−70, −57], [−56, −43], and [−42, −29]). Time-trend of ADA use was controlled using a control group of 21,859 randomly selected patients free of the event, individually matched to cases according to age, sex, and risk factors of ischemic stroke. Association between ADA use and the risk of stroke was assessed by estimating the ratio of the odds ratios (OR) of exposure evaluated in i) stroke cases and ii) in controls. Analyses were adjusted for time-varying confounders (anticoagulants, antiplatelets, prothrombotic and vasoconstrictive drugs). Results: Among the 2,612 patients identified with incident stroke, 1,250 were exposed to ADA in the risk-period and 1,060 in the reference ones. The comparison with the 5,128 and 13,165 controls exposed to ADA in the same periods yielded a ratio of adjusted ORs (aORs) of 3.12 (2.85–3.42). Analyses stratified on age, sex, and dementia showed similar results. Ratio of aORs for analyses stratified on drug was 2.51 (2.18–2.88) for domperidone, 3.62 (3.11–4.23) for metopimazine and 3.53 (2.62–4.76) for metoclopramide. Sensitivity analyses suggested the risk would be especially increased in the first days of use. Discussion/Conclusion: This nationwide self-controlled study reported an increased risk of ischemic stroke with recent ADA use. The highest increase was highlighted for metopimazine and metoclopramide use.< Réduire