Background: With its growing popularity, inclusion of image and text, and user-friendly interface, Instagram is uniquely positioned for exploring health behaviors and sources and types of informational exposure related to the human papillomavirus (HPV) vaccine. Aims: To characterize public Instagram posts about the HPV vaccine and quantify the impact of sentiment and context on engagement via likes. Method: Using Netlytic, 3,378 publicly available English-language posts were collected using the search terms "#HPV," "#HPVVaccine," and "#Gardasil." We randomly selected 1,200 posts to content analyze. Our final analytic sample included 360 posts after excluding posts whose links were no longer active (n = 221) or that were not relevant (n = 619). Results: A higher proportion of posts were pro-vaccine (55.8%) than anti-vaccine (42.2%). Pro-HPV vaccination posts were liked significantly less than anti-vaccination posts (24 vs. 86 likes; p < 0.001). More posts contained actionable information/resources (63.9%) than personal narrative elements (36.1%). Less than one in three posts (30.0%) came from health-related sources. Discussion: Pro-vaccine posts were more prevalent on Instagram, and anti-vaccine posts had higher engagement and typically included misleading information about the HPV vaccine. Personal narratives skewed toward anti-vaccine sentiments and most were produced by individual users. Pro-vaccine narratives portrayed individuals who received the vaccine, but provided limited details on vaccine experiences, starkly contrasting with the depth of details in anti-vaccine personal narrative posts. Conclusion: On Instagram, individuals and organizations have an opportunity to promote HPV vaccination by continuing to provide informational resources in addition to creating more narrative-style posts.