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Pharmacies have been endorsed as alternative vaccine delivery sites to improve vaccination rates through increased access to services. Our objective was to identify challenges and facilitators to adolescent and adult vaccination provision in pharmacy settings in the United States. We recruited 40 licensed pharmacists in states with different pharmacy vaccination laws. Eligible pharmacists previously administered or were currently administering human papillomavirus (HPV); tetanus, diphtheria, and pertussis (TDAP); or meningitis (meningococcal conjugate vaccine [MCV4]) vaccines to adolescents aged 9 to 17 years. Pharmacists participated in a semistructured survey on in-pharmacy vaccine provision. Pharmacists commonly administered vaccinations to age-eligible adolescents and adults: influenza (100%, 100%), pneumococcal (35%, 98%), TDAP (80%, 98%), MCV4 (60%, 78%), and HPV (45%, 53%). Common challenges included reimbursement/insurance coverage (28%, 78%), education of patients/parents (30%, 40%), and pharmacists' time constraints (28%, 35%). Three-quarters of pharmacists reported that vaccination rates could be increased. National efforts should expand insurance coverage for vaccine administration reimbursement and improve data information systems to optimize provision within pharmacies.