Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet, #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Since the beginning of the COVID-19 pandemic, scientists have been willing to share their results quickly to speed up the development of potential treatments and/or a vaccine. At the same time, traditional peer-review-based publication systems are not always able to process new research promptly. This has contributed to a surge in the number of medical preprints published since January 2020. In the absence of a vaccine, preventative measures such as social distancing are most helpful in slowing the spread of COVID-19. Their effectiveness can be undermined if the public does not comply with them. Hence, public discourse can have a direct effect on the progression of the pandemic. Research shows that social media discussions on COVID-19 are driven mainly by the findings from preprints, not peer-reviewed papers, highlighting the need to examine the ways medical preprints are shared and discussed online. Objective: We examine the patterns of medRxiv preprint sharing on Twitter to establish (1) whether the number of tweets linking to medRxiv increased with the advent of the COVID-19 pandemic; (2) which medical preprints were mentioned on Twitter most often; (3) whether medRxiv sharing patterns on Twitter exhibit political partisanship; (4) whether the discourse surrounding medical preprints among Twitter users has changed throughout the pandemic. Methods: The analysis is based on tweets (n=557,405) containing links to medRxriv preprint repository that were posted between the creation of the repository in June 2019 and June 2020. The study relies on a combination of statistical techniques and text analysis methods. Results: Since January 2020, the number of tweets linking to medRxiv has increased drastically, peaking in April 2020 with a subsequent cool-down. Before the pandemic, preprints were shared predominantly by users we identify as medical professionals and scientists. After January 2020, other users, including politically-engaged ones, have started increasingly tweeting about medRxiv. Our findings indicate a political divide in sharing patterns of the top-10 most-tweeted preprints. All of them were shared more frequently by users who describe themselves as Republicans than by users who describe themselves as Democrats. Finally, we observe a change in the discourse around medRxiv preprints. Pre-pandemic tweets linking to them were predominantly using the word “preprint”. In February 2020 “preprint” was taken over by the word “study”. Our analysis suggests this change is at least partially driven by politically-engaged users. Widely shared medical preprints can have a direct effect on the public discourse around COVID-19, which in turn can affect the societies’ willingness to comply with preventative measures. This calls for an increased responsibility when dealing with medical preprints from all parties involved: scientists, preprint repositories, media, politicians, and social media companies. Conclusions: Widely shared medical preprints can have a direct effect on the public discourse around COVID-19, which in turn can affect the societies’ willingness to comply with preventative measures. This calls for an increased responsibility when dealing with medical preprints from all parties involved: scientists, preprint repositories, media, politicians, and social media companies.