In 2011, Rwanda led a successful national human papillomavirus vaccine (HPV) campaign, achieving a 93% coverage rate among eligible girls. The success of the campaign has prompted us to explore the facilitators and barriers that led to its effective implementation so that it may inform vaccination rollouts in similar contextual settings. Eighteen key informants central to HPV campaign implementation in Rwanda were identified through a literature review and then were interviewed. The consolidated framework for implementation research (CFIR) informed the identification of a priori codes for our directed content analysis. Furthermore, organizational readiness for change served as a relevant theory to explain the results. The key informants listed various facilitators and barriers to the implementation of the HPV campaign. The most frequently mentioned facilitators belonged to cosmopolitanism, design quality and packaging, and leadership engagement constructs. More specifically, external partnerships, grade-based interventions, and political will were deemed the most representative and integral to the effectiveness of the intervention. Moreover, the key informants listed the barriers surrounding knowledge and beliefs as the most frequent challenges. Misconceptions surrounding the HPV vaccine, including contraceptive rumors, were described as a common deterrent to parents' decisions for their girls to get vaccinated. Overall, there was a clear assessment of the demands and needs for the scale-up of the HPV project, combined with change valence through Rwanda's consistent leadership and commitment to health promotion. The precise assessments and needs were strengthened by endorsement arising from champions, various ministries, the support of community health workers, and partnerships with funders, all of which translated into implementation effectiveness.