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Understanding how pediatric practices handle parental vaccine hesitancy is important as it impacts the efficiency and effectiveness of pediatric practices. In total, 21 semi-structured interviews with pediatric practice staff within a primary care network were conducted between May 2012 and March 2013. Thematic analysis focused on the barriers and challenges of vaccine hesitancy and strategies to reduce the burden at the practice level. Barriers and challenges of vaccine hesitancy included time constraints, administrative challenges, financial challenges and strained patient-provider relationships. Strategies to minimize the burden of vaccine hesitancy included training for vaccine counseling, screening for vaccine hesitancy prior to immunization visits, tailored vaccine counseling, and primary care provider visits for follow-up immunization. Pediatric practices reported many challenges when caring for vaccine-hesitant families. Multiple strategies were identified to reduce the burden of vaccine hesitancy, which future studies should explore to determine how effective they are in increasing vaccine acceptance in pediatric practices.