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The launch of the COVID-19 vaccination program was the largest vaccination campaign in U.S. history, with an unprecedented demand for vaccine and new vaccination providers, warranting significant education and communication efforts. NIP-INFO (nipinfo@cdc.gov) is the Centers for Disease Control and Prevention’s (CDC’s) immunization inquiry response service, and it receives inquiries for COVID-19 and routine non-COVID vaccines. A qualitative analysis of NIP-INFO’s content was performed to better characterize and understand some of the knowledge gaps and reasons that COVID-19 vaccine administration errors occur. A total of 734 COVID-19 vaccine administration error inquiries were received between January 2021 and April 2022. The most frequent inquiries related to storage (<i>n</i> = 191; 26.0%), incorrect dosage or product (<i>n</i> = 190; 25.9%), unauthorized age group (<i>n</i> = 108; 14.7%), and schedule (<i>n</i> = 105; 14.3%). Training and communication strategies are imperative to ensure proper vaccine administration and build and maintain vaccine confidence.