© 2015 Liu et al.; licensee BioMed Central. Background: Measles cases continue to occur among susceptible individuals despite the elimination of endemic measles transmission in the United States. Clustering of disease susceptibility can threaten herd immunity and impact the likelihood of disease outbreaks in a highly vaccinated population. Previous studies have examined the role of contact tracing to control infectious diseases among clustered populations, but have not explicitly modeled the public health response using an agent-based model. Methods: We developed an agent-based simulation model of measles transmission using the Framework for Reconstructing Epidemiological Dynamics (FRED) and the Synthetic Population Database maintained by RTI International. The simulation of measles transmission was based on interactions among individuals in different places: households, schools, daycares, workplaces, and neighborhoods. The model simulated different levels of immunity clustering, vaccination coverage, and contact investigations with delays caused by individuals' behaviors and/or the delay in a health department's response. We examined the effects of these characteristics on the probability of uncontrolled measles outbreaks and the outbreak size in 365 days after the introduction of one index case into a synthetic population. Results: We found that large measles outbreaks can be prevented with contact investigations and moderate contact rates by having (1) a very high vaccination coverage (≥ 95%) with a moderate to low level of immunity clustering (≤ 0.5) for individuals aged less than or equal to 18 years, or (2) a moderate vaccination coverage (85% or 90%) with no immunity clustering for individuals (≤18 years of age), a short intervention delay, and a high probability that a contact can be traced. Without contact investigations, measles outbreaks may be prevented by the highest vaccination coverage with no immunity clustering for individuals (≤18 years of age) with moderate contact rates; but for the highest contact rates, even the highest coverage with no immunity clustering for individuals (≤18 years of age) cannot completely prevent measles outbreaks. Conclusions: The simulation results demonstrated the importance of vaccination coverage, clustering of immunity, and contact investigations in preventing uncontrolled measles outbreaks.