Background: As technology has become cheaper and more accessible, health programs are adopting digital health interventions (DHI) to improve the provision of and demand for health services. These interventions are complex and require strong coordination and support across different health system levels and government departments, and they need significant capacities in technology and information to be properly implemented. Electronic immunization registries (EIRs) are types of DHI used to capture, store, access, and share individual-level, longitudinal health information in digitized records. The BID Initiative worked in partnership with the governments of Tanzania and Zambia to introduce an EIR at the sub-national level in both countries within 5 years as part of a multi-component complex intervention package focusing on data use capacity-building. Methods: We aimed to gather and describe learnings from the BID experience by conducting a framework-based mixed methods study to describe perceptions of factors that influenced scale-up of the EIR. Data were collected through key informant interviews, a desk review, EIRs, and health management information systems. We described how implementation of the EIRs fulfilled domains described in our conceptual framework and used cases to illustrate the relationships and relative influence of domains for scale-up and adoption of the EIR. Results: We found that there was no single factor that seemed to influence the introduction or sustained adoption of the EIR as many of the factors were interrelated. For EIR introduction, strong strategic engagement among partners was important, while EIR adoption was influenced by adequate staffing at facilities, training, use of data for supervision, internet and electricity connectivity, and community sensitization. Conclusions: Organizations deploying DHIs in the future should consider how best to adapt their intervention to the existing ecosystem, including human resources and organizational capacity, as well as the changing technological landscape during planning and implementation.