IntroductionWe conducted this study to quantify how health professionals use Twitter to communicate about the human papillomavirus (HPV) vaccine.MethodsWe collected 193,379 tweets from August 2014 through July 2015 that contained key words related to HPV vaccine. We classified all tweets on the basis of user, audience, sentiment, content, and vaccine characteristic to examine 3 groups of tweets: 1) those sent by health professionals, 2) those intended for parents, and 3) those sent by health professionals and intended for parents. For each group, we identified the 7-day period in our sample with the most number of tweets (spikes) to report content.ResultsOf the 193,379 tweets, 20,451 tweets were from health professionals; 16,867 tweets were intended for parents; and 1,233 tweets overlapped both groups. The content of each spike varied per group. The largest spike in tweets from health professionals (n = 851) focused on communicating recently published scientific evidence. Most tweets were positive and were about resources and boys. The largest spike in tweets intended for parents (n = 1,043) centered on a national awareness day and were about resources, personal experiences, boys, and girls. The largest spike in tweets from health professionals to parents (n = 89) was in January and centered on an event hosted on Twitter that focused on cervical cancer awareness month.ConclusionUnderstanding drivers of tweet spikes may help shape future communication and outreach. As more parents use social media to obtain health information, health professionals and organizations can leverage awareness events and personalize messages to maximize potential reach and parent engagement.