Abstract Objectives (1) Describe content and character of patient–physician human papilloma virus (HPV) vaccine discussions; (2) explore the relationship between selected characteristics and vaccine uptake. Methods Content analyses were conducted on 184 transcripts of audio-taped patient encounters with 11–26 year old female patients that occurred from August 2008 to March 2009 and contained mention of the HPV vaccine. Directed qualitative content analysis sought to identify key themes with a focus on elements related to communication. Quantitative content analysis included determination of associations between selected factors (e.g., physician specialty, communication variables, patient age) and vaccination rates. Results Communication themes identified though qualitative content analysis demonstrated potential opportunities for improvement in vaccine communication were identified. Quantitative content analysis showed twenty-eight percent of eligible patients received HPV vaccine and on average these patients were younger (17.0 vs. 19.6 years). The youngest and oldest patients were vaccinated less frequently. Conclusions Targeting age groups with lower vaccination rates may increase overall vaccine uptake. Additional quantitative analyses of patient–physician discussions about vaccine may generate further recommendations regarding optimal communication strategies for HPV vaccine counseling.