Research Objectives Nationally sponsored cancer care quality improvement efforts have been deployed in community health centers to increase breast, cervical, and colorectal cancer screening rates among vulnerable populations. Despite some immediate and short-term gains screening rates remain below national benchmark objectives. Overall improvement has been both difficult to sustain over time in some organizational settings and/or diffuse to others as repeatable best practices. One reason is that facility-level changes typically occur in dynamic organizational environments that are complex, adaptive, and unpredictable. This study seeks to better understand the factors that help shape community health center facility-level cancer screening performance over time. This study applies a computational modeling approach that combines principles of health services research, health informatics, network theory, and systems science. Methods In order to investigate the role of knowledge acquisition, retention, and sharing within the setting of the community health center and the effect of this role on the relationship between clinical decision support capabilities and improvement in cancer screening rate improvement, we employed Construct TM to create simulated community health centers using previous collected point-in-time survey data. Construct TM is a multi-agent model of network evolution. Social, knowledge, and belief networks co-evolve. Groups and organizations are treated as complex systems, thus capturing the variability in human and organizational factors. In Construct TM, individuals and groups interact communicate, learn, and make decisions in a continuous cycle. Data from the survey was used to create high-performing simulated community health centers and low-performing ones based on extent of both computer decision support use and cancer-screening rates. Results Our virtual experiment revealed that patterns of overall network symmetry, agent cohesion, and connectedness varied by community health center performance level. Visual assessment of both the agent-to-agent knowledge sharing network and agent-to-resource knowledge use network diagrams demonstrated that community health centers labeled as high performers typically showed higher levels of collaboration and cohesiveness among agent classes, faster knowledge absorption rates, and fewer unconnected agents to key knowledge resources. Conclusions and Research Implications Using the point-in-time survey data outlining community health center cancer screening practices our computational model successfully distinguished between high and low performers. Our study showed that high performance environments displayed distinctive network characteristics in patterns of interaction among agents, as well as in the access and utilization of key knowledge resources. Our study demonstrated how non-network specific data obtained from a point-in-time survey can be employed to forecast community health center performance over time and thereby enhance sustainability of long-term...