The Strategic Prevention Framework State Incentive Grant (SPF SIG) program is a national public health initiative sponsored by the U.S. Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Prevention to prevent substance abuse and its consequences. State grantees used a data-driven planning model to allocate resources to 450 communities, which in turn launched over 2,200 intervention strategies to target prevention priorities in their respective populations. An additional goal was to build prevention capacity and infrastructure at the state and community levels. This paper addresses whether the state infrastructure goal was achieved, and what contextual and implementation factors were associated with success. The findings are consistent with claims that, overall, the SPF SIG program met its goal of increasing prevention capacity and infrastructure across multiple infrastructure domains, though the mediating effects of implementation were evident only in the evaluation/monitoring domain. The results also show that an initiative like the SPF SIG, which could easily have been compartmentalized within the states, has the potential to permeate more broadly throughout state prevention systems.