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Background: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres. This study seeks to examine the effect of aspirin therapy, administered from the first trimester until 36 weeks gestation, on perinatal outcome in women with established pre-pregnancy diabetes. Our hypothesis is that aspirin therapy will reduce complications mediated by placental dysfunction, and improve perinatal outcomes. Methods: This phase III double-blinded, placebo-controlled randomized clinical trial will be conducted in seven tertiary-level perinatology centres in Ireland. Consenting participants who meet all eligibility criteria will be allocated randomly to either aspirin 150 mg once daily or matching placebo, commenced between 11 + 0 and 13 + 6 weeks. Allocation will take place electronically using software by Clininfo with randomization tables provided by the trial biostatistician. The primary outcome will be a composite clinical measure of placental dysfunction (preeclampsia, preterm birth before 34 weeks, birthweight below the 10th centile or perinatal mortality). This trial has been set up such that it is parallel in design and is a superiority study. No participants have been recruited yet. The trial has been registered with Eudra Clinical Trials - EudraCT Number 2018-000770-29. Funding for this trial was granted by the Health research Board (HRB) 1/9/2017(DIFA-2017-026). Discussion: Aspirin therapy has been investigated for the prevention of preeclampsia owing to its reduction on thromboxane production. Previous studies have failed to demonstrate a beneficial effect of aspirin on perinatal outcome amongst women with type I or type II diabetes. It is plausible that the failure to observe benefit to date, among the limited aspirin studies that have included participants with diabetes, may be a consequence of aspirin initiation too late in pregnancy to exert any effect on placentation. We believe that if aspirin is to be used for the prevention of placental dysfunction, it must be initiated before the second active phase of trophoblast invasion, which takes place from 14 weeks’ gestation onwards. No randomized trials investigating the role of aspirin in prevention of preeclampsia in pregnancies complicated by diabetes have previously initiated treatment in the first trimester, the gestational period at which it is most likely to exert an effect on placentation. Keywords: Aspirin, Pregnancy, Diabetes, Pre-eclampsia