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Negative experiences and perceptions of immunization are recognized barriers to vaccination uptake but warrant context-specific investigation. We explored barriers and enablers to immunization uptake in selected regions of Ethiopia. We conducted a formative qualitative study involving 18 focus group discussions with men and women, in-depth interviews with 23 mothers of children with varying immunization statuses, and 42 key informant interviews with religious and community leaders and health workers in eight districts in Amhara, Oromia, and Somali regions. We identified shared and regionally distinct barriers. Common barriers included limited access to services in hard-to-reach areas, low awareness of immunization, competing household responsibilities for mothers, fear of side effects, and a lack of compassionate and respectful care from health workers. Forgetting vaccination appointments was frequently reported in Amhara and Oromia. In Amhara and Somali, mistrust of vaccinators and infrequent vaccination sessions were salient challenges. In Amhara, some believed that envy or praise by vaccinators could bring harm or misfortune to children, and that vaccination should be delayed until after baptism. In Oromia, beliefs that vaccines aggravate illness and that infants should not leave home before six months of age were reported. In Somali, perceived parental negligence and beliefs that vaccines are unnecessary were described. Engaging community, traditional, and religious leaders and fathers in immunization activities in Oromia, and aligning vaccination sessions with local holidays in Amhara, emerged as promising practices. Our findings show that knowledge and perceptions of vaccines, cultural norms, service accessibility, and experiences with vaccine-preventable diseases (VPDs) and vaccination can either encourage or discourage uptake. We recommend enhancing service delivery, improving caregiver interactions, and implementing two-way community engagement involving religious and community leaders, and caregivers of fully vaccinated children, with a focus on highlighting reductions in VPD burden.<\/jats:p>","DOI":"10.1371\/journal.pgph.0006554","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:32:43Z","timestamp":1780680763000},"page":"e0006554","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgph.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Barriers to and enablers of childhood immunization uptake in Ethiopia\u2019s Amhara, Oromia, and Somali Regions: A multi-perspective qualitative study"],"prefix":"10.1371","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7711-1257","authenticated-orcid":true,"given":"Amare","family":"Zewdie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5081-1480","authenticated-orcid":true,"given":"Minyahil Tadesse","family":"Boltena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengistu","family":"Ayenew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamrat","family":"Endebu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0210-8416","authenticated-orcid":true,"given":"Melat","family":"Dereje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alemseged","family":"Abdissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirafe","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Valentine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahlil","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sostine","family":"Makunja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervat","family":"Alhaffar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-6539","authenticated-orcid":true,"given":"Catherine R.","family":"McGowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-7378","authenticated-orcid":true,"given":"Nada","family":"Abdelmagid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4831-6077","authenticated-orcid":true,"given":"Yohannes","family":"Hailemichael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"issue":"5","key":"pgph.0006554.ref001","doi-asserted-by":"crossref","first-page":"378","DOI":"10.2500\/aap.2021.42.210065","article-title":"The global burden of vaccine-preventable infectious diseases in children less than 5 years of age: Implications for COVID-19 vaccination. 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