Because U.S. human papillomavirus (HPV) vaccination rates remain low, we evaluated school nurses' knowledge, attitudes, perceptions of their role as opinion leaders, self-efficacy, intention, and professional practice regarding the HPV vaccine and determined if these variables influenced their professional practice concerning the HPV vaccine. We utilized a cross-sectional design by recruiting Ohio Association of School Nurses (OASN) members. Participants (n = 145) completed a paper survey during the OASN annual conference. Structural equation modeling was used to examine the proposed model. Our model yielded a well-fitting solution, ?[superscript 2] = 1.118 (degrees of freedom = 2, p = 0.57). Knowledge had positive effects on intention and self-efficacy. Attitude had a positive effect on perception of role as opinion leaders. Intention to provide HPV vaccine education had a positive effect on professional practice. To develop school nurses' practice, interventions should center on increasing knowledge, attitudes, and intention toward providing HPV vaccine education.