Background: School nurses and personnel play a vital role in promoting the human papillomavirus (HPV) vaccine. The purpose of this study was to identify factors associated with school nurses' and personnel's professional practice to provide parents with HPV vaccine information and to encourage parents to vaccinate their child against HPV. Methods: School nurses and personnel from Ohio and Missouri completed a survey to assess their professional practice in providing HPV vaccine information and encouraging parents to vaccinate their child against HPV. Independent variables included demographics, HPV knowledge/attitudes, perceptions of their as an opinion leader for the HPV vaccine, self-efficacy to provide vaccine education, and perception of school district support. Results: Providing parents with HPV vaccine information was predicted by age, role within the school, grade-serving, knowledge, perceptions, self-efficacy, and district support; accounting for 38% of the variance (p < 0.000, R[superscript 2] = 0.38). Encouraging parents to vaccinate their child against HPV was predicted by perception, self-efficacy, and grade-serving; accounting for 39% of the variance (p < 0.000, R[superscript 2] = 0.39). Conclusions: To enhance school nurses' and personnel's professional practice, interventions should focus on nurses' and personnel's perception of their role as opinion leaders and self-efficacy to provide HPV education and vaccine recommendation.