Intermittent Preventive Treatment for Malaria in Infants (IPTi) is a new strategy which aims to combine the short-term protection of chemoprophylaxis with the long-term protection of naturally-acquired immunity to reduce morbidity from malaria infections during infancy. The Bill and Melinda Gates Foundation requested that the Institute of Medicine (IOM) conduct an independent assessment of the IPTi efficacy studies using sulfadoxine-pyrimethamine (IPTi-SP) that have been previously conducted by the IPTi Consortium. The IOM convened a committee to evaluate the evidence concerning IPTi-SP, which included addressing issues related to its utility and safety, as well as program management aspects of IPTi. The resulting letter report contains the findings, conclusions, and recommendations of the IOM committee. Overall, the committee found that the evidence presented makes IPTi-SP a promising public health strategy to diminish the morbidity from malaria infections, especially for the incidence of clinical malaria, among infants at high risk who reside in areas of high- or moderate-intensity transmission and is worthy of continued investment. The committee also cautioned that during large-scale implementation problems such as drug supply and logistics; monitoring and resistance; and community acceptance and reaction to IPTi-SP could arise. To maximize the greatest public health impact, the committee advised that these issues would best be addressed in an appropriate local context.