To contrast the advantages and limitations of using medication, diagnostic, and cost data to prospectively identify candidates for care management programs.Risk scores from prior-cost information and a set of clinically based predictive models (PMs) derived from diagnostic and medication data sources, as well as from a combination of all 3 data sources, were assigned to a national sample of commercially insured, non-elderly adults (n = 2,259,584). Clinical relevance of risk groups and statistical performance using future costs as the outcome were contrasted across the PMs.Compared with prior cost, diagnostic and medication-based PMs identified high-risk groups with a higher burden of clinically actionable characteristics. Statistical performance was similar and in some cases better for the clinical PMs compared with prior cost. The best classification accuracy was obtained with a comprehensive model that united diagnostic, medication, and prior-cost risk factors.Clinically based PMs are a better choice than prior cost alone for programs that seek to identify high-risk groups of patients who are amenable to care management services.