BackgroundKnowledge about the risks of drugs during pregnancy is continuously evolving due to the frequent publication of a large number of epidemiological studies. Systematic reviews and meta-analyses therefore need to be regularly updated to reflect these advances. To improve dissemination of this updated information, we developed an initiative of real-time full-scale living meta-analyses relying on an open online dissemination platform (www.metapreg.org).MethodAll living meta-analyses performed in this project will be conducted in accordance with this master protocol after adaptation of the search strategy. A systematic literature search of PubMed and Embase will be performed. All analytical studies (e.g., cohort, case-control, randomized studies) reporting original empirical findings on the association between in utero exposure to drugs and adverse pregnancy outcomes will be included. Study screening and data extraction will be performed in a semi-automation way supervised by a biocurator. A risk of bias will be assessed using the ROBINS-I tools. All clinically relevant pregnancy adverse outcomes (malformations, stillbirths, neuro-developmental disorders, pre-eclampsia, etc.) available in the included studies will be pooled through random-effects meta-analysis. Heterogeneity will be evaluated byI2statistics.DiscussionOur living systematic reviews and subsequent updates will inform the medical, regulatory, and health policy communities as the news results evolve to guide decisions on the proper use of drugs during the pregnancy.Systematic review registrationOpen Science Framework (OSF) registriesSupplementary InformationThe online version contains supplementary material available at 10.1186/s13643-023-02256-8.