Background Detecting Adverse Drug Events (ADEs) is an emerging research area, attracting great interest in the research community. Better anticipatory management of predisposing factors has considerable potential to improve outcomes. Automatic extraction of ADEs using Natural Language Processing (NLP) has a great potential to significantly facilitate efficient and effective distillation of such knowledge, to better understand and predict risk of adverse events. Methods This systematic review follows the six-stage including the literature from 6 databases (Embase, Medline, Web Of Science, ACM Guide to Computing Literature, IEEE Digital Library and Scopus). Following the title, abstract and full-text screenings, characteristics and main findings of the included studies and resources will be tabulated and summarized. The risk of bias and reporting quality was assessed using the PROBAST tool 1 . Results We developed our search strategy and collected all relevant publications. As of October 2023, we have completed the first two stages of the systematic review. We identified 178 studies for inclusion through the academic literature search (where data was extracted from 118 papers). Further refinement of the eligibility criteria and data extraction has been ongoing since August 2022. Conclusion In this systematic review, we will identify and consolidate information and evidence related to the use and effectiveness of existing NLP approaches and tools for automatically detecting ADEs from free text (discharge summaries, General Practitioner notes, social media, etc.). Our findings will improve the understanding of the current landscape of the use of NLP for extracting ADEs. It will lead to better anticipatory management of predisposing factors with the potential to improve outcomes considerably. Our results will also be valuable both to NLP researchers developing methods to extract ADEs and to translational/clinical researchers who use NLP for this purpose and in healthcare in general.