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Up to 4 million people in Tanzania are at risk for the parasitic disease onchocerciasis. A treatment program, Community-Directed Treatment with Ivermectin (CDTI), has made significant gains in prevention and treatment. Understanding factors affecting participation could help boost treatment coverage and sustain gains made in controlling onchocerciasis in endemic areas.To explore community-perceived factors related to participation in and sustainability of the CDTI program in southwest Tanzania.Multilevel triangulation design using surveys, focus group discussions (FGDs), and semistructured interviews to collect data in two villages in the Morogoro Rural District of Tanzania. In total, 456 villagers participated in the survey and 42 in FDGs. Five community-directed distributors (CDDs) and three community health workers were interviewed.High levels of awareness of onchocerciasis (90%) and methods of prevention and treatment (95%) were reported. Over 75% of participants knew how ivermectin was distributed and 74% have taken the drug. Over 90% of villagers knew that distribution of the drug was for treatment and prevention. Only 43% knew the cause of onchocerciasis. Through FGDs, villagers reported barriers to participation, including lack of comprehensive understanding of the disease, fears of medication, distrust of the method determining dose, lack of health education materials, insufficient CDD-resident communication, and inflexible drug distribution mechanisms.Sustaining programs without supporting growth of CDDs and reinforcing education of communities could lead to a decrease in treatment and an increase in the public health threat. This research uncovered a need for more effective community education and sensitization.Understanding barriers to participation in community-based programs can assist public health and community health nurses and key stakeholders including Ministries of Health and local and regional health systems in the development of education and support materials to enhance health literacy and encourage program participation.