Women with HIV in high-income settings have increasingly expressed a desire to breastfeed their infants. Although national guidelines now acknowledge this choice, detailed recommendations are not available. We describe the approach to managing care for breastfeeding women with HIV at a single large-volume site in the United States. We convened an interdisciplinary group of providers to establish a protocol intended to minimize the risk of vertical transmission during breastfeeding. Programmatic experience and challenges are described. A retrospective chart review was conducted to report the characteristics of women who desired to or who did breastfeed between 2015 and 2022 and their infants. Our approach stresses the importance of early conversations about infant feeding, documentation of feeding decisions and management plans, and communication among the health care team. Mothers are encouraged to maintain excellent adherence to antiretroviral treatment, maintain an undetectable viral load, and breastfeed exclusively. Infants receive continuous single-drug antiretroviral prophylaxis until 4 weeks after cessation of breastfeeding. From 2015 to 2022, we counseled 21 women interested in breastfeeding, of whom 10 women breastfed 13 infants for a median of 62 days (range, 1-309). Challenges included mastitis (N = 3), need for supplementation (N = 4), maternal plasma viral load elevation of 50-70 copies/mL (N = 2), and difficulty weaning (N = 3). Six infants experienced at least 1 adverse event, most of which were attributed to antiretroviral prophylaxis. Many knowledge gaps remain in the management of breastfeeding among women with HIV in high-income settings, including approaches to infant prophylaxis. An interdisciplinary approach to minimizing risk is needed.