Trade-offs may exist between investments to promote health system strengthening, such as investments in facilities and training, and the rapid scale-up of HIV/AIDS services. We analyzed trends in expenditures to support the prevention of mother-to-child transmission of HIV in Kenya under the President's Emergency Plan for AIDS Relief (PEPFAR) from 2005 to 2010. We examined how expenditures changed over time, considering health system strengthening alongside direct treatment of patients. We focused on two organizations carrying out contracts under PEPFAR: the Elizabeth Glaser Pediatric AIDS Foundation and FHI360 (formerly Family Health International), a nonprofit health and development organization. We found that the average unit expenditure, or the spending on goods and services per mother living with HIV who was provided with antiretroviral drugs, declined by 52 percent, from $567 to $271, during this time period. The unit expenditure per mother-to-infant transmission averted declined by 66 percent, from $7,117 to $2,440. Meanwhile, the health system strengthening proportion of unit expenditure increased from 12 percent to 33 percent during the same time period. The analysis suggests that PEPFAR investments in prevention of mother-to-child transmission of HIV in Kenya became more efficient over time, and that there was no strong evidence of a trade-off between scaling up services and investing in health systems.