Objectives HPV vaccination at the recommended ages of 11–12 is highly effective yet has stalled well below the goal of 80% of the population. We evaluated a statewide practice-based communication intervention (tools: brochures, posters, online training for providers and resources for parents, video game for preteens) to persuade parents, preteens and providers to vaccinate against HPV. The 9-month intervention started May 1, 2015. Methods We compared vaccine initiation and completion rates over three 9-month periods (baseline, intervention, post-intervention) between practices enrolled in the intervention and a comparable comparison group. All practices reported to the North Carolina Immunization Registry (NCIR) and had at least 100 11- and 12-year-olds who had not completed the HPV vaccine series. Of 175 eligible practices, the 14 intervention practices included 19,398 individuals and the 161 comparison practices included 127,896 individuals. An extended Cox model was used to test the intervention effect. Results The intervention had a significant effect on both initiation and completion during the intervention and post-intervention periods; the estimated hazard ratio (HR) for initiation was 1.17 (p =.004) during the intervention and 1.11 (p =.005) post-intervention. Likewise, completion during the intervention period was 17% higher in intervention practices, after controlling for baseline differences. This effect increased in the post-intervention period to 30% higher (p =.03). Conclusions Individuals in the intervention practices were 17% more likely to initiate and complete HPV vaccination than in the comparison practices during the intervention period and the effect was sustained post-intervention. This intervention is promising for increasing rates of HPV vaccination at ages 11–12.