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Recent legislation requires reducing Medicare payments to hospitals with higher than expected 30-day readmission rates, but there is no consensus strategy to identify patients who should optimally be targeted with care coordination services to mitigate this risk. To determine which hospital and patient factors predict variation in all discharge hospital readmission rates, a 5% sample of all Medicare fee-for-service beneficiaries with continuous Part A and B coverage was examined for the first 9 months of 2008 in combination with other administrative data available to the Centers for Medicare and Medicaid Services. We included age, sex, race, dual-eligibility status, number of comorbid conditions, geographic region, hospital case mix, and reason for entitlement in the multiple regression model to assess how they influenced the 30-day readmission rate. Beneficiaries with 10 or more chronic conditions were more than 6 times more likely to be readmitted than beneficiaries with 1 to 4 chronic conditions. These beneficiaries represent only 8.9% of all Medicare beneficiaries (31.0% of all hospitalizations), but they were responsible for 50.2% of all readmissions. The 31.8% of beneficiaries with 5 to 9 chronic conditions (55.5% of all hospitalizations) had the second highest odds ratio (2.5) and were responsible for 45% of all readmissions. Journal of Hospital Medicine 2013;8:639–641. © 2013 Society of Hospital Medicine