© 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Background. Although the increasing number of recommended immunizations is essential for patients infected with human immunodeficiency virus (HIV), the potentially uncompensated costs of expanded immunizations will present significant challenges for clinics and health systems serving HIV-infected patients. Methods. We estimated costs of providing Gardasil, Prevnar, and Zostavax to eligible patients at a US Ryan White Part C academically affiliated HIV clinic in 2013. Clinic expenditures were calculated using vaccine price and administrative fees. Revenue was calculated using insurance reimbursement data for vaccination and administration. Three scenarios were used: 100% uptake of vaccines, adjusted uptake based on published rates, and adjusted reimbursement according to pre-Affordable Care Act (ACA) insurance status. Results. 2887 patients (27% Medicare, 13% Alabama Medicaid, 26% Commercial, 34% Uninsured), received care with wide variation in immunization reimbursement ($0 to $210) by insurance and vaccine. The net yield (revenue minus expenditure) was calculated for each vaccine. Prevnar was most costly: annual net yield of -$60 691. Provision of all 3 vaccines would lead to a net yield of -$97 122. Adjusting for reduced uptake led to annual clinic losses of $44 119. Using pre-ACA reimbursement for immunization of the uninsured led to reduced clinic losses (-$62 326), attributable to reimbursement via Ryan White funds. Conclusions. A cost analysis of 3 vaccines shows great variation in insurance coverage, with potential losses of almost $100 000 for one HIV clinic if eligible patients received vaccinations in one calendar year. Adequate, cost neutral reimbursement should be instituted if medical providers and health systems are to achieve Advisory Committee on Immunization Practices immunization recommendations for both HIV positive and negative adults.