Elders with chronic illness are hospitalized more often than those without major chronic disease, and nearly one-fifth of hospitalizations result in re-admission within 30 days of discharge from the hospital. Care transition management programs address chronic disease complexity to reduce unnecessary hospitalization, improve quality of care, and reduce medical expense. This report describes how informatics influenced the transformation of a regional managed care organization from one focused on specific chronic disease prevalence to one targeting population-specific chronic conditions based on complexity. The key implication of these results is that population-based informatics can amplify the impact of programs designed to improve quality and prevent avoidable admissions and, at the same time, speed the rate of translation of evidence-based interventions to entire populations. This approach demonstrated an effective, efficient way to translate evidence-based research to the Medicare population, smoothing the transition back into the community, and preventing avoidable hospital admissions.