The use of Twitter by healthcare organizations is an effective means of disseminating medical information to the public. However, the content of tweets can be influenced by various factors, such as health emergencies and medical breakthroughs. In this study, we conducted a discourse analysis to better understand how public and private healthcare organizations use Twitter and the factors that influence the content of their tweets. Data were collected from the Twitter accounts of five private pharmaceutical companies, two US and two Canadian public health agencies, and the World Health Organization from 1 January 2020, to 31 December 2022. The study applied topic modeling and association rule mining to identify text patterns that influence the content of tweets across different Twitter accounts. The findings revealed that building a reputation on Twitter goes beyond just evaluating the popularity of a tweet in the online sphere. Topic modeling, when applied synchronously with hashtag and tagging analysis can provide an increase in tweet popularity. Additionally, the study showed differences in language use and style across the Twitter accounts’ categories and discussed how the impact of popular association rules could translate to significantly more user engagement. Overall, the results of this study provide insights into natural language processing for health literacy and present a way for organizations to structure their future content to ensure maximum public engagement.