Oral pre-exposure prophylaxis (PrEP) reduces HIV acquisition risk from sex by 99% and from injection drug use by ≥74% when used as recommended. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a goal of 21.2 million persons using (initiating or continuing) PrEP globally in 2025. In 2016, CDC, with the U.S. President's Emergency Plan for AIDS Relief, joined ministries of health to implement PrEP globally. PrEP is beneficial for persons at substantial risk for acquiring HIV, including but not limited to key populations, which include female sex workers, men who have sex with men, persons in prisons and other enclosed settings, persons who inject drugs, and transgender persons. Annual country targets were used to guide scale-up. In 2023, CDC supported 856,816 PrEP initiations, which represents nearly one quarter of the 3.5 million persons globally who either initiated or continued PrEP that year. During 2017-2023, CDC supported PrEP initiations for 2,278,743 persons, 96.0% of whom were in sub-Saharan Africa. More than one half (64.0%) were female and 44.9% were aged 15-24 years. Overall, CDC achieved 118.7% of its PrEP initiation targets for the 7-year period. Among PrEP initiations for key populations, the majority in sub-Saharan Africa were female sex workers, whereas in Southeast Asia, Eurasia, and the Americas, the majority were men who have sex with men. Continued rapid scale-up is needed to meet the UNAIDS goal to end HIV as a public health threat.