With hundreds of millions of active users generating almost a half of a billion tweets each day, Twitter has solidified itself as one of the most popular websites in today’s digital world. Because of this popularity, companies seeking to leverage the large audience have gravitated toward Twitter. This study examines how the Fortune 500 uses Twitter by analyzing 9,122 corporate tweets and 1,509 user replies through the use of content analysis. Examined factors include interactivity (non-interactive vs. reactive vs. interactive), company type (B2B vs. B2C), and user reply valence (positive vs. neutral vs. negative). Company response time to user replies is also investigated. The study results point to interactive tweets generating the most engagement. B2Cs not only respond faster to user replies but also generate more engagement than B2Bs. Negative replies can decrease engagement for B2Bs and B2Cs, but the influence on B2Bs is more profound. Companies responded the fastest to negative replies followed by positive replies and neutral replies, respectively. Thus, a company should assess its own business practices, target audience, and ability to perform customer service before creating a social media account such as Twitter.