BackgroundEnsuring reduction in transmission of lymphatic Filariasis (LF) and addressing the compliance of people to mass drug administration (MDA) has led to renewed efforts in the field. School-based health education (SBHE) intervention, considered a cost-effective strategy with potential to reach the wider public through young people, was adopted as a strategy for social mobilization. This study assessed SBHE perceptions, implementation barriers, and factors in the supporting environment as well as its efficiency to successfully change LF MDA-related knowledge and practice.MethodsThis mixed methods study was conducted in four sites of Lalitpur district, Nepal. Classroom-based interactive health education sessions were used as the main intervention strategy in the study. In total, 572 students were assigned to intervention and control groups. Questionnaires were distributed before and after the intervention. Mann-Whitney and McNemar tests were used for analysis. Focus-group discussions with teachers and students and in-depth interviews with the district LF program manager as well as Education Office and school management authorities were conducted. Qualitative thematic analysis approach was adopted.ResultsIntervention curriculum played a significant role in increasing children’s knowledge and practice (p<0.001). Barriers for school-based interventions were budget constraints, human resource deficiencies, lack of opportunities to conduct practical classes under the curriculum, and lack of collaboration with parents. Supportive factors were training provision, monitoring and evaluation practice, adequate facilities and equipment, positive parental attitudes, presence of interested teachers and students, and prioritization by program implementers.ConclusionEffective program planning practices such as proper fiscal management, human resource management, training mechanisms, and efforts to promote practical classes and coordination with parents are required to develop and institutionalize the intervention. Effective learning and a supportive school environment appear to be important components to support implementation. The SBHE intervention is a feasible and promising intervention for accelerating compliance towards MDA to eliminate LF.