BackgroundSustaining evidence-based interventions (EBIs) is an ongoing challenge for dissemination and implementation science in public health and social services. Characterizing the relationship among human resource capacity within an agency and subsequent population outcomes is an important step to improving our understanding of how EBIs are sustained. Although human resource capacity and population outcomes are theoretically related, examining them over time within real-world experiments is difficult. Simulation approaches, especially agent-based models, offer advantages that complement existing methods.MethodsWe used an agent-based model to examine the relationships among human resources, EBI delivery, and population outcomes by simulating provision of an EBI through a hypothetical agency and its staff. We used data from existing studies examining a widely implemented HIV prevention intervention to inform simulation design, calibration, and validity. Once we developed a baseline model, we used the model as a simulated laboratory by systematically varying three human resource variables: the number of staff positions, the staff turnover rate, and timing in training. We tracked the subsequent influence on EBI delivery and the level of population risk over time to describe the overall and dynamic relationships among these variables.ResultsHigher overall levels of human resource capacity at an agency (more positions) led to more extensive EBI delivery over time and lowered population risk earlier in time. In simulations representing the typical human resource investments, substantial influences on population risk were visible after approximately 2 years and peaked around 4 years.ConclusionsHuman resources, especially staff positions, have an important impact on EBI sustainability and ultimately population health. A minimum level of human resources based on the context (e.g., size of the initial population and characteristics of the EBI) is likely needed for an EBI to have a meaningful impact on population outcomes. Furthermore, this model demonstrates how ABMs may be leveraged to inform research design and assess the impact of EBI sustainability in practice.Electronic supplementary materialThe online version of this article (10.1186/s13012-018-0767-0) contains supplementary material, which is available to authorized users.