Abstract Background: Human papilloma virus (HPV) is the most common sexually transmitted infection in the US, with an annual incidence rate of approximately 14 million people. The HPV vaccine has been demonstrated to be highly effective in the prevention of HPV infection and HPV associated diseases. This study aims to evaluate the impact of HPV vaccine on the prevalence of HPV infection in the US. Methods: We conducted secondary data analysis of the National Health and Education Survey (NHANES) for trends in HPV infection from 2003 to 2016. Analysis were grouped into a pre-HPV vaccine implementation (2003 – 2006) cohort including 4064 females, aged 18 – 59 years; and a post-HPV vaccine implementation (2007 – 2016) cohort which included 10718 females, aged 18 – 59 years. Further analysis of HPV infection prevalence, pre and post HPV vaccine implementation, stratified by sociodemographic characteristics were conducted. Results: The prevalence of HPV infection prior to HPV vaccine implementation was 43.98% (95 CI 42.71% - 46.58%) compared to 40.55% (95 C.I 40.55% - 40.56%) in the post-HPV vaccine implementation era. Among females with HPV infections in the post-HPV vaccine implementation cohort 82.6% (95% CI 80.41% - 83.42%) were unvaccinated. In both cohorts, black females had a significantly higher prevalence of HPV with a prevalence rate of 18.56% (95% CI 18.23% - 20.56%) in the pre-HPV vaccine implementation cohort, and 15.61% (95% CI 14.82 – 19.4%) in the post-HPV vaccine implementation cohort. Females with less than high school education had a higher prevalence of HPV in the pre and post- HPV vaccine implementation cohorts with prevalence rates of 25.77% (95% CI 23.44% – 28.72%) and 24.96% (95% CI 23.41% - 25.67%) respectively. Conclusions: The results suggest that HPV infection prevalence has declined since the implementation of HPV vaccine to US national immunization program. Our findings highlight disparities in HPV infection prevalence by race and educational status, and these patterns are in keeping with HPV associated disease such as warts and HPV-associated cancers.