INTRODUCTION: The Global Vaccine Action Plan and the Regional Immunization Action Plan of the Americas call for countries to improve immunization data quality. Immunization information systems, particularly electronic immunization registries (EIRs), can help to facilitate program management and increase coverage. However, little is known about efforts to develop and implement such systems in low- and middle-income countries. We present the experiences of Mexico and Peru in implementing EIRs. METHODS: We conducted case studies of an EIR in Mexico and of a population registry in Peru. Information was gathered from technical documents, stakeholder focus groups, site visits, and semi-structured interviews of national stakeholders. We organized findings into narratives that emphasized challenges and lessons learned. RESULTS: Mexico built one of the world's first EIRs, incorporating novel features such as local-level tracking of patients; however, insufficient resources and poor data registration practices led to the system's discontinuation. Peru created an information system to improve affiliation to social programs, including the immunization program and quality of demographic data. Mexico's experience highlights lessons in failed sustainability of an EIR and a laudable effort to reform a country's information system. Peru's demonstrates that attempts to improve health and other data may strengthen health systems, including immunization data. Major challenges in information system implementation and sustainability in Peru and Mexico related to funding, clear governance structures, and resistance among health workers. DISCUSSION: These case studies reinforce the need for countries to ensure adequate funding, plans for sustainability, and health worker capacity-building activities before implementing EIRs. They also suggest new approaches to implementation, including economic incentives for sub-national administrative levels and opportunities to link efforts to improve immunization data with other health and political priorities. More information on best practices is needed to ensure the successful adoption and sustainability of immunization registries in low- and middle-income countries.