Abstract Purpose We sought to examine the sentiment and themes of marijuana-related chatter on Twitter sent by influential Twitter users and to describe the demographics of these Twitter users. Methods We assessed the sentiment and themes of a random sample (n = 7,000) of influential marijuana-related tweets (sent from February 5, 20114, to March 5, 2014). Demographics of the users tweeting about marijuana were inferred using a social media analytics company (Demographics Pro for Twitter). Results Most marijuana-related tweets reflected a positive sentiment toward marijuana use, with pro-marijuana tweets outnumbering anti-marijuana tweets by a factor of greater than 15. The most common theme of pro-marijuana tweets included the Tweeter stating that he/she wants/plans to use marijuana, followed by tweeting about frequent/heavy/or regular marijuana use, and that marijuana has health benefits and/or should be legalized. Tweeters of marijuana-related content were younger and a greater proportion was African-American compared with the Twitter average. Conclusions Marijuana Twitter chatter sent by influential Twitter users tends to be pro-marijuana and popular among African-Americans and youth/young adults. Marijuana-related harms may afflict some individuals; therefore, our findings should be used to inform online and offline prevention efforts that work to target individuals who are most at risk for harms associated with marijuana use.