INTRODUCTION: The Pan American Health Organization (PAHO) created the ProVac Initiative in 2004 with the goal of strengthening national technical capacity to make evidence-based decisions on new vaccine introduction, focusing on economic evaluations. In view of the 10th anniversary of the ProVac Initiative, this article describes its progress and reflects on lessons learned to guide the next phase. METHODS: We quantified the output of the Initiative's capacity-building efforts and critically assess its progress toward achieving the milestones originally proposed in 2004. Additionally, we reviewed how country studies supported by ProVac have directly informed and strengthened the deliberations around new vaccine introduction. RESULTS: Since 2004, ProVac has conducted four regional workshops and supported 24 health economic analyses in 15 Latin American and Caribbean countries. Five Regional Centers of Excellence were funded, resulting in six operational research projects and nine publications. Twenty four decisions on new vaccine introductions were supported with ProVac studies. Enduring products include the TRIVAC and CERVIVAC cost-effectiveness models, the COSTVAC program costing model, methodological guides, workshop training materials and the OLIVES on-line data repository. Ten NITAGs were strengthened through ProVac activities. DISCUSSION: The evidence accumulated suggests that initiatives with emphasis on sustainable training and direct support for countries to generate evidence themselves, can help accelerate the introduction of the most valuable new vaccines. International and Regional Networks of Collaborators are necessary to provide technical support and tools to national teams conducting analyses. Timeliness, integration, quality and country ownership of the process are four necessary guiding principles for national economic evaluations to have an impact on policymaking. It would be an asset to have a model that offers different levels of complexity to choose from depending on the vaccine being evaluated, the availability of data, and the time frame of the decision. CONCLUSION: Decision support for new vaccine introduction in low- and middle-income countries is critical to maximizing the efficiency and impact of vaccination programs. Global technical cooperation will be required. In the future, PAHO and WHO have an opportunity to expand the reach of the ProVac philosophy, models, and methods to additional regions and countries requiring real-time support. The ProVac Global Initiative is proposed as an effective mechanism to do so.