OBJECTIVES: To measure the effectiveness of preventive interventions against hospital readmissions in at-risk Medicaid populations of five Medicaid managed care organizations (MCOs) serving four states (Pennsylvania, Louisiana, South Carolina, and Nebraska) and the District of Columbia. METHODS: One-year follow-up analysis of member data was performed following intervention period from January 1 to December 31, 2014. Sixty operational and communication-based interventions targeting members, providers, and AmeriHealth Caritas associates were implemented to reduce 30-day all-cause hospital readmissions and expenditures in at-risk Medicaid members with one or more dominant chronic conditions or a single moderate chronic condition of asthma in the 2013 baseline period. Thirty-day hospitalization readmission rates (utilization per thousand members per year) were calculated at baseline and at one-year post-intervention. RESULTS: The majority of participants for all plans were female (53%), English speakers (91%), Supplemental Security Income recipients (59%), and Black (42%) or White (39%). Most subjects were ≤18 years (41%), followed by 40–64 years (37%), 18–39 years (20%) and ≥65 years (1.9%). AmeriHealth Caritas achieved a statistically significant enterprise-wide reduction in plan size-weighted 30-day readmission rates of 10.1% (P<0.01) in 2014 versus 2013, along with an associated 4.8% reduction in readmission expenditures resulting in an estimated cost savings of $2.7 million USD. Three of the five MCOs displayed statistically significant reductions in hospital readmissions (Southeastern Pennsylvania, P=0.03; Louisiana and South Carolina, P<0.01). Despite considerable sociodemographic variation, all five plans met or exceeded the corporate goal of a 4% reduction in hospital readmissions. Only one MCO displayed statistically significant reductions in hospital readmission expenditures (Louisiana; P<0.01) and another MCO displayed a trend toward significance (South Carolina; P=0.06). CONCLUSIONS: Multifaceted MCO-implemented interventions significantly reduced hospital readmissions—and sometimes associated expenditures—in at-risk Medicaid subjects.