Summary Objectives : To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select best papers published in 2019. Method : A bibliographic search using a combination of MeSH descriptors and free-text terms on CRI was performed using PubMed, followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. After peer-review ranking, a consensus meeting between the two section editors and the editorial team was organized to finally conclude on the selected three best papers. Results : Among the 517 papers, published in 2019, returned by the search, that were in the scope of the various areas of CRI, the full review process selected three best papers. The first best paper describes the use of a homomorphic encryption technique to enable federated analysis of real-world data while complying more easily with data protection requirements. The authors of the second best paper demonstrate the evidence value of federated data networks reporting a large real world data study related to the first line treatment for hypertension. The third best paper reports the migration of the US Food and Drug Administration (FDA) adverse event reporting system database to the OMOP common data model. This work opens the combined analysis of both spontaneous reporting system and electronic health record (EHR) data for pharmacovigilance. Conclusions : The most significant research efforts in the CRI field are currently focusing on real world evidence generation and especially the reuse of EHR data. With the progress achieved this year in the areas of phenotyping, data integration, semantic interoperability, and data quality assessment, real world data is becoming more accessible and reusable. High quality data sets are key assets not only for large scale observational studies or for changing the way clinical trials are conducted but also for developing or evaluating artificial intelligence algorithms guiding clinical decision for more personalized care. And lastly, security and confidentiality, ethical and regulatory issues, and more generally speaking data governance are still active research areas this year.