The objective was to combine cost analysis and participatory research to identify actionable cost-saving opportunities in public health services for sexually transmitted infections (STI). This study used a mixed-methods approach of analyzing Florida public health data, combined with participatory research approaches to data collection including quantitative web-based surveys, qualitative in-depth interviews, and group discussions. Florida surveillance and administrative data on STIs and county health department (CHD) costs of services for 2012 were analyzed in addition to primary data collected from all Florida CHDs during 2014 and 2015. Variations in STI service delivery practices were the primary variables of concern. Variations in practices, rather than demographic factors such as size of county or STI rates, were associated with variations in cost. Five identified variations in practices were rated for cost savings, no or minimal adverse health impact, and ease of implementation. Following discussion of the ratings by CHDs, texting STI test results was ranked highest for quality improvement implementation initiatives. This study provides a compelling example of how in-depth qualitative and quantitative follow-up research focused on discovery and development with the practice community provides critical insights for interpreting administrative data and drawing accurate reality-based conclusions. The research design was intended to be a highly adaptive research approach that adjusts to the political and technical circumstances of delivering public health services. The extensive stakeholder engagement throughout all phases the study enables this research to address and overcome potential barriers and challenges to actionable findings.