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ObjectiveTo explore the most important public health information system database integration project success factors to include: technological, organizational, project-specific, or external.MethodsThis study involved a cross-case design. Cases were identified through literal replication logic and screened through a survey and review of available literature. Study participants were interviewed through hour-long sessions steered by a semi-structured guide. Survey responses, interview transcripts and available documents were coded and analyzed deductively, and matrices were developed to illustrate relationships.ResultsLeadership among the project’s participants is the most important integration project success factor. This leadership factor manifests in the following ways. Executive sponsors champion the initiative. Informaticians facilitate communication and system requirement collection. Program directors contribute substantive energy to the project and remove obstacles. Some other factors also contribute to project success. For example, strong Financial Management and Support promotes project initiation. Technological aspects impact the final product’s quality. Utilizing formal project management techniques, particularly the Agile software development methodology, contributes to successful project resolution by ensuring daily operational effectiveness.DiscussionThe principal finding illustrates important contributions by project leaders, transcending those of the executive sponsor. Other participants, notably informaticians and program directors, substantially contribute to the project’s success. Additionally, the Agile software development methodology is emerging as a successful approach to project management for these and related projects.ConclusionInvesting in the leadership and project management skills of database integration project participants could improve the success of future projects. State health department staff considering these projects should carefully select project participants and train them accordingly.